Publications by authors named "Yener Koc"

93 Publications

Comparison of lung ultrasound and other volumetric methods in peritoneal dialysis patients.

Medicine (Baltimore) 2021 Jan;100(3):e23856

Nephrology Department, Medical Faculty, Cumhuriyet University, Sivas, Turkey.

Abstract: Although many alternative methods are present, maintaining ideal volume status in peritoneal dialysis (PD) patients still rely on clinical evaluation due to lack of an evidence-based method. Lung ultrasound (LUS) is a new method for evaluation of hidden congestion in this group.LUS findings and its relationship with other volumetric methods are investigated in this observational cross-sectional study.In this observational cross sectional study, LUS was performed to all PD patients and compared with symptoms of hypervolemia, physical examination, vascular endothelial growth factor-C (VEGF-C), and N-terminal pro-brain natriuretic peptide levels, chest radiography, echocardiography, bioelectrical impedance analysis.Data of 21 PD patients were evaluated. There was correlation between number of B lines and VEGF-C levels (r = 0.447, P = .042), daily urine output (r = 0.582, P = .007) and left ventricle mass index (r = -0.456, P = .038). Correlations with all other parameters were not significant. Daily urine output and VEGF-C levels were significantly different when B lines were grouped into 2 according to the median level (P < .05 for all).This is the widest spectrum study looking for LUS findings and other volumetric parameters in a small PD cohort. LUS might be useful to evaluate hidden hypervolemia. Its correlation with VEGF-C level is a novel finding.
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http://dx.doi.org/10.1097/MD.0000000000023856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837871PMC
January 2021

Clinical outcomes of COVID-19 in hemodialysis patients in the city of Zonguldak, Turkey.

Int Urol Nephrol 2021 Jan 15. Epub 2021 Jan 15.

Division of Nephrology, Department of Internal Medicine, Sivas Cumhuriyet University Medical Faculty, Sivas, Turkey.

Purpose: Patients on maintenance hemodialysis are vulnerable to viral infections like COVID-19 because of the low chance of obedience and complying with rules besides the need for transfer to distant dialysis facilities. We investigated the impact and clinical effect of treatment of COVID-19 in dialysis patients.

Methods: We included patients on maintenance hemodialysis at different healthcare facilities in Zonguldak city. With the diagnosis of the first infected HD case, all other patients who shared the same session were screened. Hospitalized and clinically confirmed cases were included. COVID-19 diagnosis was made based on clinical, biochemical along radiologic findings.

Results: 34 (F/M:19/15, mean age 62 ± 13.2 years, dialysis duration 66.9 ± 57.7 months, length of hospital stay 16.2 ± 7.9 days) were diagnosed with COVID-19 infection. The prevalence of COVID-19 was found to be 18.4% of our exposed population. 38.2% of our patients were initially diagnosed by CT screening while asymptomatic. 35.3% had a fever as the first presenting symptom. Lymphopenia was the most common laboratory finding. Except for one, all had at least one comorbidity. Out of 12 (35.3%) patients admitted to ICU 6(17.6%) died. The deceased patients were older, presented with lower serum albumin and lymphocyte count, and had higher CRP and fibrinogen levels. High CRP level on admission was the only significant predictor of mortality.

Conclusion: Early detection will lower mortality. In this study, with a low prevalence of COVID-19, the importance of early screening of both symptomatic and asymptomatic patients was shown to be highly important. Further studies are still needed to find out the most appropriate medical management.
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http://dx.doi.org/10.1007/s11255-020-02781-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809887PMC
January 2021

Pentraxin-2 is Associated with Renal Fibrosis in Patients Undergoing Renal Biopsy.

Clinics (Sao Paulo) 2020 26;75:e1809. Epub 2020 Oct 26.

University of Health Sciences, Sisli Hamidiye Etfal Teaching and Research Hospital, Istanbul, Turkey.

Objectives: Progressive renal disease is characterized by histological changes in the kidney and fibrosis is a common outcome. Renal biopsy is the only diagnostic tool to evaluate these histopathological changes. Pentraxin-2 (PTX-2) is an anti-inflammatory constitutive plasma protein associated with the innate immune system. Recently, as a biomarker, the circulating level of PTX-2 is shown to be decreased in chronic fibrotic diseases. In this study, we aimed to investigate the relationship between renal fibrosis severity and serum PTX-2 levels in patients undergoing renal biopsy.

Methods: This cross-sectional study included 45 patients and 16 healthy individuals (HIs). The severity of renal fibrosis was evaluated according to the Banff and Sethi scoring systems by the same pathologist. PTX-2 was measured by an enzyme-linked immunosorbent assay and compared with the demographical, clinical, biochemical, and histopathological data of the patients and HIs.

Results: PTX-2 levels were lower in the biopsy group than in the HI group (p=0.12). Patients with moderate renal fibrosis had significantly lower serum PTX-2 levels than those in patients with minimal and mild fibrosis (p=0.017 and p=0.010, respectively). PTX-2 concentrations were correlated with serum albumin (r=0.30, p=0.016), and were negatively correlated with serum creatinine levels (rho=-0.42, p=0.01) and body mass index (r=-0.32, p=0.011).

Conclusions: The results indicated that PTX-2 levels are significantly lower in patients with renal fibrosis than HIs, and declining further in patients with severe fibrosis.
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http://dx.doi.org/10.6061/clinics/2020/e1809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561072PMC
October 2020

Post-transplantation cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation from HLA-identical sibling donors: A retrospective analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Cancer 2021 Jan 29;127(2):209-218. Epub 2020 Oct 29.

Hematology Department, Hôpital Saint Antoine, Service d'Hématologie et Thérapie Cellulaire, Paris, France.

Background: Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Addition of antithymocyte globulin (ATG) or post-transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents reduces GVHD in different donor settings.

Methods: We compared the outcomes of adults with acute myeloid leukemia undergoing allo-HSCT from HLA-identical sibling donors after the use of PTCY (n = 197) or ATG (n = 1913).

Results: Patients in the PTCY group were younger than those in the ATG group (median age, 47 vs 54 years; P < .01). Peripheral blood was the most frequently used stem cell source, being significantly more frequent in the ATG group than in the PTCY group (95% vs 70% P < .01). The conditioning regimen was more frequently myeloablative in the PTCY group than in the ATG group (59% vs 48%; P < .01). Time to neutrophil engraftment was shorter in the ATG group than in the PTCY group (17 vs 20 days; P < .01). No differences were observed according to the other transplantation outcomes, except for chronic GVHD of all grades and extensive chronic GVHD at 2 years, which were significantly lower in the ATG group compared with the PTCY group (P < .02).

Conclusion: PTCY is feasible in an HLA-identical sibling setting, and despite similar outcomes, ATG may be associated with lower incidence of chronic GVHD.
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http://dx.doi.org/10.1002/cncr.33255DOI Listing
January 2021

Unexpectedly High Prevalence of Low Alpha-Galactosidase A Enzyme Activity in Patients with Focal Segmental Glomerulosclerosis.

Clinics (Sao Paulo) 2020 28;75:e1811. Epub 2020 Sep 28.

Department of Nephrology, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey.

Objectives: Fabry disease (FD) is a rare disease associated with sphingolipid accumulation. Sphingolipids are components of plasma membranes that are important in podocyte function and accumulate in various glomerular diseases such as focal segmental glomerulosclerosis (FSGS). Both FD and FSGS can cause podocyte damage and are classified as podocytopathies. In this respect, FD and FSGS share the same pathophysiologic pathways. Previous screening studies have shown that a significant proportion of end-stage renal disease (ESRD) patients receiving hemodialysis (HD) have unsuspected FD, and the prevalence of low alpha-galactosidase A (αGLA) enzyme activity in these patients is higher than that in the normal population. We aimed to compare αGLA enzyme activity in patients with biopsy-proven FSGS and ESRD receiving HD.

Methods: The records of 232 patients [62 FSGS (F/M: 33/29); 170 HD (M/F: 93/79)] were evaluated retrospectively. The screening was performed based on the αGLA enzyme activity on a dried blood spot, with the confirmation of plasma LysoGb3 levels, and the known GLA mutations were tested in patients with low enzyme activities. The two groups were compared using these parameters.

Results: The mean level of αGLA enzyme activity was found to be lower in FSGS patients than in the HD group (2.88±1.2 μmol/L/h versus 3.79±1.9 μmol/L/h, p<0.001). There was no significant relationship between the two groups with regard to the plasma LysoGb3 levels (2.2±1.22 ng/ml versus 1.7±0.66 ng/ml, p: 0.4). In the analysis of GLA mutations, a D313Y mutation [C(937G>T) in exon p] was found in one patient from the FSGS group.

Conclusions: We found that αGAL activity in patients with FSGS is lower than that in patients undergoing HD. The low enzyme activity in patients with FSGS may be explained by considering the similar pathogenesis of FSGS and FD, which may also lead to sphingolipid deposition and podocyte injury.
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http://dx.doi.org/10.6061/clinics/2020/e1811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510945PMC
October 2020

Impact of total body irradiation- vs chemotherapy-based myeloablative conditioning on outcomes of haploidentical hematopoietic cell transplantation for acute myelogenous leukemia.

Am J Hematol 2020 Jul 13. Epub 2020 Jul 13.

Saint Antoine Hospital, INSERM UMR 938, Université Pierre et Marie Curie, Paris, France and EBMT Paris study office / CEREST-TC, Paris, France.

The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic cell transplantation (haplo-HCT) is unknown. We studied the outcomes of total body irradiation (TBI) vs chemotherapy (CT) based MAC regimens in acute myeloid leukemia (AML) patients. The study included 1008 patients who underwent first haplo-HCT with post-transplant cyclophosphamide, following TBI (N = 89, 9%) or CT (n = 919, 91%) based MAC. Patients in the TBI cohort were younger (median age, 38 vs 47 years, P < .01) and more likely to receive BM graft (57% vs 43%, P = .01). Two-year overall chronic GVHD (cGVHD) incidence was 42% vs 27% (P < .01) and extensive cGVHD incidence was 9% vs 12% (P = .33) in TBI and CT cohorts, respectively. Graft failure was reported in two (2%) TBI- and 65 (7%) CT-MAC recipients (P = .08). Death from veno-occlusive disease was reported in one (3%) TBI and 11 (3%) CT patients who died during the study period. In the multivariate analysis, TBI was associated with increased risk for overall cGVHD (hazard ratio = 1.95, 95% confidence interval:1.2-3.1, P < .01) compared to CT-based MAC. The choice of conditioning regimen did not impact relapse incidence, leukemia-free survival, non-relapse mortality, overall survival or GVHD-relapse-free survival in multivariate analysis. In conclusion, major transplant outcomes were not statistically different between TBI-based MAC and CT-based MAC in patients with AML after haplo-HCT/PTCy.
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http://dx.doi.org/10.1002/ajh.25934DOI Listing
July 2020

A Comparison of the BEAM and MITO/MEL Conditioning Regimens for Autologous Hematopoietic Stem Cell Transplantation in Hodgkin Lymphoma: An Analysis of Efficiency and Treatment-Related Toxicity.

Clin Lymphoma Myeloma Leuk 2020 10 21;20(10):652-660. Epub 2020 May 21.

Baskent University Adana Adult Bone Marrow Transplantation Center, Adana, Turkey.

Background: Approximately half of patients with relapsed chemosensitive disease achieve robust responses with BEAM (BCNU, etoposide, cytarabine, and melphalan) and autologous stem cell rescue. The scarcity of comparative studies further limits alternative treatment protocols, such as the MITO/MEL (mitoxantrone, melphalan) protocol.

Patients And Methods: In this retrospective multicenter study, we compared the BEAM and MITO/MEL regimens used before autologous hematopoietic stem cell transplantation (ASCT) in terms of efficacy and side effects in patients with Hodgkin lymphoma. Data met international accreditation rules. Before ASCT, 108 patients received the MITO/MEL, and 34 patients received the BEAM.

Results: The median follow-up time was 36 months in the MITO/MEL group (range, 3-178) and 23 months in the BEAM group (range, 4-99). After ASCT, the 3-year expected overall survival and disease-free survival rates were 86.1% and 86.1% for the MITO/MEL group and 91.3% and 76.5% for the BEAM group, respectively. Although 50% of patients developed febrile neutropenia attacks in the MITO/MEL group, this rate was 91.1% in the BEAM group. The grade II and higher rates of hepatic, renal, gastrointestinal, and cardiac toxicities were similar in both groups. However, the rate of pulmonary toxicity was determined to be 1.9% in the MITO/MEL group and 29.4% in the BEAM group (P < .001).

Conclusion: The MITO/MEL conditioning regimen seems to be as effective as the BEAM regimen but has better tolerability in terms of pulmonary toxicity and may be used as an alternative option if necessary, depending on the comorbidity status of the patient.
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http://dx.doi.org/10.1016/j.clml.2020.05.009DOI Listing
October 2020

Comparing transplant outcomes in ALL patients after haploidentical with PTCy or matched unrelated donor transplantation.

Blood Adv 2020 05;4(9):2073-2083

Department of Hematology, European Society for Blood and Marrow Transplantation (EBMT) Paris Study Office/Centros de Referência em Saúde do Trabalhador, Hôpital Saint Antoine, INSERM, Paris, France.

We compared outcomes of 1461 adult patients with acute lymphoblastic leukemia (ALL) receiving hematopoietic cell transplantation (HCT) from a haploidentical (n = 487) or matched unrelated donor (MUD; n = 974) between January 2005 and June 2018. Graft-versus-host disease (GVHD) prophylaxis was posttransplant cyclophosphamide (PTCy), calcineurin inhibitor (CNI), and mycophenolate mofetil (MMF) for haploidentical, and CNI with MMF or methotrexate with/without antithymoglobulin for MUDs. Haploidentical recipients were matched (1:2 ratio) with MUD controls for sex, conditioning intensity, disease stage, Philadelphia-chromosome status, and cytogenetic risk. In the myeloablative setting, day +28 neutrophil recovery was similar between haploidentical (87%) and MUD (88%) (P = .11). Corresponding rates after reduced-intensity conditioning (RIC) were 84% and 88% (P = .47). The 3-month incidence of grade II-IV acute GVHD (aGVHD) and 3-year chronic GVHD (cGVHD) was similar after haploidentical compared with MUD: myeloablative conditioning, 33% vs 34% (P = .46) for aGVHD and 29% vs 31% for cGVHD (P = .58); RIC, 31% vs 30% (P = .06) for aGVHD and 24% vs 29% for cGVHD (P = .86). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 44% and 51% with haploidentical and MUD (P = .56). Corresponding rates after RIC were 43% and 42% (P = .6). In this large multicenter case-matched retrospective analysis, despite the limitations of a registry-based study (ie, unavailability of key elements such as minimal residual disease testing), our analysis indicated that outcomes of patients with ALL undergoing HCT from a haploidentical donor were comparable with 8 of 8 MUD transplantations.
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http://dx.doi.org/10.1182/bloodadvances.2020001499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218425PMC
May 2020

Bone marrow versus mobilized peripheral blood stem cell graft in T-cell-replete haploidentical transplantation in acute lymphoblastic leukemia.

Leukemia 2020 10 11;34(10):2766-2775. Epub 2020 May 11.

EBMT ALWP Office, Saint Antoine Hospital, Paris, France.

The ideal stem cell graft source remains unknown in haploidentical haematopietic cell transplantation (haplo-HCT) with posttransplantation cyclophosphamide (PTCy). This study compared outcomes of bone marrow (BM) versus peripheral blood (PB) stem cell graft for haplo-HCT in acute lymphoblastic leukemia (ALL). A total of 314 patients with ALL (BM-157; PB-157) were included in this study. The cumulative incidence of engraftment at day 30 was higher in the PB group compared with BM (93% vs. 88%, p < 0.01). The incidences of acute graft-versus-host disease (GVHD) and chronic GVHD were not significantly different between the study cohorts. In the multivariate analysis, there were tendencies toward a higher incidence of grade II-IV acute GVHD (hazard ratio (HR) = 1.52, p = 0.07), chronic GVHD (HR = 1.58, p = 0.05), and nonrelapse mortality (NRM) (HR = 1.66, p = 0.06) in patients receiving PB versus BM graft, respectively. The use of PB grafts was associated with lower leukemia-free survival (LFS) (HR = 1.43, p = 0.05), overall survival (OS) (HR = 1.59, p = 0.02), and GVHD-free, relapse-free survival (GRFS) (HR = 1.42, p = 0.03) compared with BM grafts. There was no difference in relapse incidence (HR = 1.23, p = 0.41) between the study groups. In conclusion, use of BM graft results in better survival after haplo-HCT with PTCy in patients with ALL, compared with PB stem cell graft.
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http://dx.doi.org/10.1038/s41375-020-0850-9DOI Listing
October 2020

Comparison of Exit-Site Infection Frequency in Continuous Ambulatory Peritoneal Dialysis and Automated Peritoneal Dialysis Patients: A Single-Center Experience.

Sisli Etfal Hastan Tip Bul 2019 3;53(4):385-388. Epub 2019 Sep 3.

Department of Nephrology, Istanbul Bilim University Faculty of Medicine, Istanbul, Turkey.

Objectives: Catheter exit-site infection (ESI) is generally caused by skin flora. Continuous ambulatory peritoneal dialysis (CAPD) patients have more contact with their catheters than automated peritoneal dialysis (APD) patients as a result of performing multiple exchanges per day. The aim of the present study was to compare the frequency of ESIs between these 2 peritoneal dialysis (PD) modalities.

Methods: PD patients from 2001 to 2015 were enrolled in the study. Patients transferred from CAPD to APD were excluded. All of the data were collected retrospectively. The rate of ESI occurrence and culture results in the CAPD and APD groups were compared.

Results: The data of 280 patients were evaluated. APD patients represented 23.2% of the study cohort. Prevalence of peritonitis was 87.6% if a patient had an ESI and 50.7% if there was no ESI (p=0.000). The frequency of ESI was similar between the 2 peritoneal dialysis modalities (p=0.343). There was a statistically significant difference in the causative organism of infection between the 2 groups (p=0.021).

Conclusion: The ESI rate was similar in the CAPD and APD patients though CAPD requires more exchanges, and therefore there is more contact with the catheter. All PD patients, regardless of the treatment modality used, are expected to perform exchanges according to standard rules for connecting the catheter to the PD solution bag. As long as patients observe these guidelines, there would appear to be no increased ESI risk related specifically to the modality.
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http://dx.doi.org/10.14744/SEMB.2019.54837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192299PMC
September 2019

Post-transplant cyclophosphamide after matched sibling, unrelated and haploidentical donor transplants in patients with acute myeloid leukemia: a comparative study of the ALWP EBMT.

J Hematol Oncol 2020 05 6;13(1):46. Epub 2020 May 6.

Department of Hematology, Hopital Saint Antoine, Sorbonne University, Paris, France.

Background: The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft-versus-host disease (GVHD) in the haploidentical (Haplo) transplant setting and is being increasingly used in matched sibling (MSD) and matched unrelated (MUD) transplants. There is no information on the impact of donor types using homogeneous prophylaxis with PTCy.

Methods: We retrospectively compared outcomes of adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) who received a first allogeneic stem cell transplantation (SCT) with PTCy as GVHD prophylaxis from MSD (n = 215), MUD (n = 235), and Haplo (n = 789) donors registered in the EBMT database between 2010 and 2017.

Results: The median follow-up was 2 years. Haplo-SCT carried a significantly increased risk of acute grade II-IV GVHD (HR 1.6; 95% CI 1.1-2.4) and NRM (HR 2.6; 95% CI 1.5-4.5) but a lower risk of relapse (HR 0.7; 95% CI 0.5-0.9) that translated to no differences in LFS (HR 1.1; 95% CI 0.8-1.4) or GVHD/relapse-free survival (HR 1; 95% CI 0.8-1.3). Interestingly, the use of peripheral blood was associated with an increased risk of acute (HR 1.9; 95% CI 1.4-2.6) and chronic GVHD (HR 1.7; 95% CI 1.2-2.4) but a lower risk of relapse (HR 0.7; 95% CI 0.5-0.9).

Conclusions: The use of PTCy in patients with AML in CR1 receiving SCT from MSD, MUD, and Haplo is safe and effective. Haplo-SCT had increased risk of acute GVHD and NRM and lower relapse incidence but no significant difference in survival.
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http://dx.doi.org/10.1186/s13045-020-00882-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201995PMC
May 2020

Post-transplant cyclophosphamide versus anti-thymocyte globulin for graft-versus-host disease prevention in haploidentical transplantation for adult acute lymphoblastic leukemia.

Haematologica 2020 04 30. Epub 2020 Apr 30.

Saint Antoine Hospital and Université Pierre et Marie Curie, Paris, France.

Graft-versus-host disease (GVHD) prophylaxis for unmanipulated haploidentical hematopoietic cell transplantation (haplo-HCT) include post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG). Utilizing EBMT registry, we compared ATG versus PTCy based GVHD prophylaxis in adult acute lymphoblastic leukemia (ALL) patients undergoing haplo-HCT. Included were 434 patients; ATG (n=98) and PTCy (n=336). Median follow-up was ~2 years. Baseline characteristics were similar between the groups except that the ATG-group was more likely to have relapsed/refractory ALL (P=0.008), non-TBI conditioning (P<0.001), peripheral blood graft source (P=<0.001) and transplanted at an earlier time-period (median year of HCT 2011 vs. 2015). The 100-day grade II-IV and III-IV acute-GVHD was similar between ATG and PTCy, as was 2-year chronic-GVHD. On multivariate analysis (MVA), leukemia-free survival (LFS) and overall survival (OS) was better with PTCy compared to ATG prophylaxis. Relapse incidence (RI) was lower in the PTCy group (P=0.03), while non-relapse mortality (NRM) was not different. Advanced disease and lower performance score were associated with poorer LFS and OS and advanced disease with inferior GVHD-free/relapse-free survival (GRFS). Peripheral grafts were associated with higher GVHD compared to bone marrow grafts. In ALL patients undergoing unmanipulated haplo-HCT, PTCy for GVHD prevention resulted in lower RI and improved LFS and OS compared to ATG.
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http://dx.doi.org/10.3324/haematol.2020.247296DOI Listing
April 2020

CD34+ cell dose effects on clinical outcomes after T-cell replete haploidentical allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia using peripheral blood stem cells. A study from the acute leukemia working Party of the European Society for blood and marrow transplantation (EBMT).

Am J Hematol 2020 08 1;95(8):892-899. Epub 2020 May 1.

Saint-Antoine Hospital, Paris, France.

Previous observations have reported controversial conclusions regarding cell dose and survival endpoints after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a retrospective analysis on 414 adult patients (median age 54 years, range, 18-74 years) with acute myeloid leukemia (AML) in first and second complete remission. They received a T-cell replete allogeneic HSCT from haploidentical donors, using peripheral blood stem cells, between 2006-2018. Median number of infused CD34+ was 6.58 × 10 /kg (range, 2.2-31.2 × 10 /kg). Graft-vs-host disease (GVHD) prophylaxis was post-transplant cyclophosphamide in 293 patients and anti-lymphocyte serum in 121 patients. Conditioning was myeloablative in 179 patients and reduced-intensity in 235 patients. After a median follow-up of 23.3 months (range, 12.1-41.8 months), 2-year overall survival (OS) was 64.5% (95% CI 59.3%-69.7%) with leukemia-free survival (LFS) of 57.3% (95% CI 51.8%-62.7%) and non-relapse mortality (NRM) of 23.3% (95% CI 19%-27.7%). Grades III-IV acute GVHD day+100 incidence was 14.6% while extensive chronic GVHD was 14.4% at 2-years. Thirteen (3.2%) patients experienced graft failure. We found the optimal CD34+/kg threshold defining high (n = 334) vs low cell dose (n = 80) at 4.96 × 10 . Recipients of >4.96 × 10 /kg CD34+ cells experienced less NRM (Hazard ratio [HR] 0.48; 95% CI 0.30-0.76) and prolonged LFS (HR 0.63; 95% CI 0.43-0.91) and OS (HR 0.60; 95% CI 0.40-0.88) compared to those in the lower cell dose cohort. Larger cohort studies are needed to confirm these findings.
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http://dx.doi.org/10.1002/ajh.25826DOI Listing
August 2020

Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for T Cell Acute Lymphoblastic Leukemia: A Report from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party.

Biol Blood Marrow Transplant 2020 05 9;26(5):936-942. Epub 2020 Jan 9.

Department of Hematology-BMT, Hopital St Antoine, Paris, France.

Allogeneic hematopoietic cell transplantation (HCT) is recommended in high-risk patients with T cell acute lymphoblastic leukemia (T-ALL). For patients without an HLA-identical donor, haploidentical (haplo-) HCT is becoming the leading source of stem cell donation. However, data are scarce on predictive factors for outcome in that setting. We identified 122 adults (20% female; median age, 31 years; range, 18 to 68 years) with T-ALL who underwent haplo-HCT with post-transplantation cyclophosphamide (ptCy) between 2010 and 2017. The median duration of follow-up of living patients was 23 months. The 2-year incidences of relapse and nonrelapse mortality were 45% and 21%, respectively. The 2-year leukemia-free survival (LFS), overall survival (OS), and graft-versus-host disease, relapse-free survival (GRFS) were 34%, 42%, and 27%, respectively. The 2-year LFS and OS were highly influenced by disease status at transplantation, being 49% and 55%, respectively, for patients in first complete remission (CR1); 34% and 50%, respectively, for those in second CR (CR2); and 8% and 12%, respectively, for patients with active disease. On multivariate analysis, only disease status was found to affect LFS and OS. Transplantation in CR2 negatively affected LFS, whereas active disease at the time of haplo-HCT negatively affected LFS and OS. In conclusion, haplo-HCT with ptCy produced encouraging results in this challenging disease, particularly when performed in patients in CR. Despite the limitation of the small sample size, our results were not affected by the type of conditioning, calling into question the need for total body irradiation-based myeloablative conditioning in that setting.
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http://dx.doi.org/10.1016/j.bbmt.2020.01.003DOI Listing
May 2020

Haploidentical transplantation and posttransplant cyclophosphamide for treating aplastic anemia patients: a report from the EBMT Severe Aplastic Anemia Working Party.

Bone Marrow Transplant 2020 06 16;55(6):1050-1058. Epub 2019 Dec 16.

Hematology-Transplantation Department, Saint-Louis Hospital, Paris, France.

In the absence of an HLA-matched donor, the best treatment for acquired aplastic anemia patients refractory to immunosuppression is unclear. We collected and analyzed data from all acquired aplastic anemia patients who underwent a haploidentical transplantation with posttransplant cyclophosphamide in Europe from 2011 to 2017 (n = 33). The cumulative incidence of neutrophil engraftment was 67% (CI: 51-83%) at D +28 and was unaffected by age group, stem cell source, ATG use, or Baltimore conditioning regimen. The cumulative incidence of grades II-III acute GvHD was 23% at D +100, and limited chronic GvHD was 10% (0-20) at 2 years, without cases of grade IV acute or extensive chronic GvHD. Two-year overall survival was 78% (64-93), and 2-year graft-versus-host disease-free survival was 63% (46-81). In univariate analysis, the 2-year OS was higher among patients who received the Baltimore conditioning regimen (93% (81-100) versus 64% (41-87), p = 0.03), whereas age group, stem cell source, and ATG use had no effect. Our results using unmanipulated haploidentical transplantation and posttransplant cyclophosphamide for treating refractory AA patients are encouraging, but warrant confirmation in a prospective study with a larger number of patients and longer follow-up.
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http://dx.doi.org/10.1038/s41409-019-0773-0DOI Listing
June 2020

Role of Age and Hematopoietic Cell Transplantation-Specific Comorbidity Index in Myelodysplastic Patients Undergoing an Allotransplant: A Retrospective Study from the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation.

Biol Blood Marrow Transplant 2020 03 21;26(3):451-457. Epub 2019 Oct 21.

Hopital St. Louis, Paris, France.

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option for myelodysplastic syndromes (MDSs) but is severely limited by nonrelapse mortality (NRM), especially in this mostly older population. Comorbidity assessment is crucial to predict NRM and often assessed with the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI). Moreover, the impact of age on NRM still remains a matter of debate. In recent years, the age at which transplants are made has been progressively increasing, and patients with comorbidities have become more common. Extricating the respective roles of age and comorbidities in toxic mortality is all the more important. This study by the European Group for Blood and Marrow Transplantation registry included 1245 adult patients who underwent a first allogeneic stem cell transplantation for MDSs between 2003 and 2014. Overall, 4-year NRM and overall survival were 32% and 47%, respectively. When considered as continuous predictors, HCT-CI score and age were associated with an increased hazard ratio (HR) for NRM. In multivariate analysis, age band (HR, 1.13; 95% CI, 1.02 to 1.25; P= .016), HCT-CI ≥3 (HR, 1.34; 95% CI, 1.04 to 1.73; P = .022), and Karnofsky Performance Status ≤80 (HR, 2.03; 95% CI, 1.52 to 2.73; P< .0001) were significantly predictive of a worse NRM. In our large cohort, both comorbidities, evaluated by the original HCT-CI score, and chronological age significantly affected NRM. Thus, age should be part of the transplant decision-making process and should be integrated in future scoring systems predicting outcomes of HSCT in MDSs.
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http://dx.doi.org/10.1016/j.bbmt.2019.10.015DOI Listing
March 2020

Influence of donor type, stem cell source and conditioning on outcomes after haploidentical transplant for lymphoma - a LWP-EBMT study.

Br J Haematol 2020 03 9;188(5):745-756. Epub 2019 Sep 9.

ICO - Hospital Duran i Reynals, Barcelona, Spain.

Haploidentical stem cell transplantation (haploSCT) is becoming a major transplant modality for lymphoma. To assess the effects of donor characteristics, stem cell source and conditioning on outcomes, we identified 474 adults with Hodgkin (HL; 240), peripheral T-cell (PTCL; 88), diffuse large B-cell (77), mantle cell (40) or follicular lymphoma (FL; 29), who received haploSCT with post-transplant cyclophosphamide. Median follow-up of alive patients was 32 months. On multivariate analysis, acute graft-versus-host disease (GVHD) grade 2-4 was lower with offspring donors or bone marrow cells, whereas extensive chronic GVHD was higher in partial response at haploSCT or when using sisters, haploidentical donors beyond first degree, or female donors in male patients. Progression-free survival (PFS) was better for FL, HL and PTCL, whereas overall survival (OS) was better for HL and PTCL. Complete remission at haploSCT improved PFS and OS whereas these were negatively affected by cytomegalovirus donor positive/recipient positive status. No other donor characteristics (age, gender, human leucocyte antigen mismatch, ABO incompatibility) affected PFS or OS except use of haploidentical donors beyond first degree, which negatively affected OS. PFS and OS are mostly influenced by disease status and lymphoma subtype, supporting the use of any first degree haploidentical family member as a donor.
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http://dx.doi.org/10.1111/bjh.16182DOI Listing
March 2020

Clinical Prognosis of Renal Retransplant Patients: A Single-Center Experience.

Transplant Proc 2019 Sep;51(7):2274-2278

Unit of Renal Transplantation, Department of General Surgery, Istanbul Bilim University Medical Faculty, Istanbul, Turkey.

Background: Retransplantation is a treatment option in patients with end-stage renal failure due to graft loss. Outcomes of these patients due to high immunologic risk remain unclear. The aim of this study was to evaluate outcomes of renal retransplantation patients retrospectively.

Methods: Renal retransplant patients in our unit were evaluated retrospectively between 2010 and 2018. Patients' demographic characteristics, primary diseases, the causes of prior graft loss, immunologic status, desensitization protocols, the induction and maintenance treatments, the complications during the follow-up period, numbers of acute rejections, and the clinical prognosis were all detected from the patients' files.

Results: We retrospectively evaluated 17 patients who underwent a second or third renal allograft. Of these, 16 received a second and the remaining 1 patient received a third renal allograft. Immunologically, all of the 17 patients had negative flow cytometry crossmatch, 1 patient had a positive complement-dependent cytotoxicity crossmatch (Auto 12%), 16 patients had positive panel reactive antibody, the median HLA-mismatch was 3.5, and the score of donor-specific antibody relative intensity score (RIS) was 6.4 ± 6.3. Ten pretransplant patients had desensitization treatment. While scores for HLA-MM and HLA-RIS in the patients who had a desensitization therapy were determined higher, no statistical difference was observed (respectively, P = .28 and .55). No acute rejection episode developed. BK virus DNA viremia was detected in 4 patients during the posttransplant 6th month. We observed no patient death or no graft loss during the follow-up period.

Conclusion: Although the retransplant patients who had a graft loss previously have high immunologic risks, retransplantation is reliable in these patients, but they should be followed up carefully in terms of BKV nephropathy.
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http://dx.doi.org/10.1016/j.transproceed.2019.03.053DOI Listing
September 2019

Incisional Complications and Cosmetic Evaluation After Hand-assisted Retroperitoneoscopic Donor Nephrectomy.

Transplant Proc 2019 Sep;51(7):2215-2220

Department of Kidney and Pancreas Transplantation, Istanbul Bilim University Sisli Florence Nightingale Hospital, Istanbul, Turkey.

Purpose: Hand-assisted retroperitoneoscopic (HARP) donor nephrectomy prevents major complications, but incision site complications may be more frequent in hand-assisted approach. We evaluated long-term incisional complication rates and cosmetic outcomes after HARP donor nephrectomy in our series.

Materials And Methods: A total of 609 donors who underwent nephrectomy between February 2009 and June 2016 were invited for physical examination and face-to-face interview. A total of 209 donors (35.3%) participated to the study. Sex, age, body mass index (BMI), mean follow-up period, incision-related outcomes of cosmesis, and postoperative complications were evaluated. Body image scale (BIS) and cosmetic scale (CS) (scar test) questionnaires were applied. Higher cosmesis and body image scores indicated greater satisfaction.

Results: A total of 191 donors had paramedian (91.4%), and 18 donors had Pfannenstiel incision (8.6%); 121 donors were female (57.9%). The donor mean age and BMI were 49.1 (SD, 1.8) years and 29.7 (SD, 5.1), respectively. Body mass index was significantly lower in the Pfannenstiel group (P < .001). The mean BIS score was 18.9 (SD, 1.8), and the CS questionnaire score was 19.3 (SD, 4,7). The BIS score was significantly better in donors with Pfannenstiel incisions (P < .001), but there was no statistical significance in CS score. The total rate of wound infection was 4.8%, and rate of incisional hernia was 4.8%. The rate of incisional hernia was more frequent in donors with paramedian incision (5.2%), but there was no statistical significance. Six donors (2.9%) required rehospitalization because of incision site complications.

Conclusion: Hand-assisted retroperitoneoscopic donor nephrectomy avoids intra-abdominal complications, but rate of incision site complications can be higher in hand-assisted procedure. The donors were convinced from the cosmetic outcome after HARP donor nephrectomy. The ones who had Pfannenstiel incision had better satisfaction according to BIS score.
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http://dx.doi.org/10.1016/j.transproceed.2019.01.162DOI Listing
September 2019

Kidney Transplantation Outcomes in Temporarily Protected Syrian Patients With End-Stage Renal Failure in Turkey.

Transplant Proc 2019 Sep 26;51(7):2279-2282. Epub 2019 Jul 26.

Nephrology Department, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey.

Background: Approximately 6.3 million Syrian people migrated to other countries due to war since 2011. There are more than 3.5 million Syrian people living in Turkey under temporary protection. Syrian people receive free health care in Turkey, including kidney transplantation. Our institution started a kidney transplantation program about 3 years ago. It is the first institution performing living, related kidney transplantation for Syrian patients with end-stage renal failure.

Methods: All living, related kidney transplantations to Turkish and Syrian patients from the beginning of our transplantation program until September 2018 were enrolled in this study. Donor and recipient characteristics, induction and maintenance immunosuppression, length of hospital stay, creatinine values at first week and first month, treatment incompatibility, and graft survival were evaluated.

Results: Of the 25 living, related kidney transplantations 20% were Syrian. Three of 5 Syrian recipients were in the pediatric age group. None of the Syrian transplantations were preemptive, while half of the Turkish transplantations were preemptive (P = .005). Immunosuppression protocols, creatinine values, length of hospital stay, and graft survival rates were similar between groups. None of the Syrian recipients had treatment incompatibility (0%), unlike the Turkish recipients (15%).

Conclusion: Outcomes of kidney transplantation for Syrian recipients are similar to those of Turkish recipients. Having this no-cost facility is great for Syrian kidney failure patients. The number of transplantations for Syrian patients under temporary protection in Turkey is expected to increase in the future, with these favorable results and easy to access, free health care facilities.
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http://dx.doi.org/10.1016/j.transproceed.2019.01.194DOI Listing
September 2019

Outcome of Desensitization Therapy in Immunologically High-Risk Kidney Transplantation: Single-Center Experience.

Transplant Proc 2019 Sep 26;51(7):2268-2273. Epub 2019 Jul 26.

Unit of Renal Transplantation, Department of General Surgery, Istanbul Bilim University Medical Faculty, Istanbul, Turkey.

Aim: Sensitization to HLA antigens creates an immunologic barrier, linked to an increased risk of antibody-mediated rejection and poorer graft survival, that remains a persistent and often impenetrable deterrent to transplantation. Desensitization can improve transplantation rates in broadly sensitized kidney transplant recipients. We aimed to compare the clinical outcomes of immunologic high-risk kidney recipients who had desensitization treatment with the outcomes of those who did not.

Materials And Methods: We retrospectively evaluated patients who underwent desensitization protocol due to immunologic risk between 2010 and 2018. Living-donor transplantation patients with panel reactive antibody positivity, retransplantation, donor specific antibody, and/or single antigen bead positivity were included in the study. We excluded deceased-donor transplantation recipients. Demographic data (age, sex, etiology of end-stage renal disease, blood transfusions, pregnancy, etc), immunologic status (HLA-mismatch [HLA-MM], panel reactive antibody, donor specific antibody, etc), induction and maintenance of immunosuppressive medications, and complications (all-cause hospitalizations, episodes of acute rejections, etc) were noted. We compared data and clinical outcomes of patients who had desensitization (Group 1) with data and clinical outcomes of patients who had not had desensitization (Group 2).

Findings: There were 124 living-kidney donors (49 female, mean age 43.7 ± 12.2 years, mean body mass index [BMI] 25.8 ± 5.8 kg/m, mean follow-up time 20.9 ± 14.6 months). Thirty-four of these patients (25 female, mean age 43.7 ± 12.5 years, mean follow-up time 26.1 ± 17.7 months, mean BMI 27 ± 6.5 kg/m) had desensitization treatment (rituximab+plasmapheresis for 19 patients, rituximab for 11 patients, rituximab+plasmapheresis+intravenous immunoglobulin for 4 patients). Ninety patients (24 female, mean age 43.7 ± 12.2 years, mean follow-up time 18.9 ± 12.9 months, mean BMI 25.3 ± 5.4 kg/m) had not had desensitization. There was no statistical difference between groups for age, sex, hepatitis serology, history of blood transfusion, history of pregnancy, or history of dialysis (P < .05 for all parameters). While scores for HLA-MM and HLA-relative intensity scale (RIS) were 2.7 ± 1.6 and 7.86 ± 6.2, respectively, in Group 1, in Group 2 the same scores were 2.1 ± 1.1 and 3.6 ± 2.5, respectively (P: .053 and .03). Delayed graft function, acute rejection episodes, and hospitalizations were similar between groups (P: .47, .29, and .34, respectively). Follow-up time and length of hospitalization were longer in Group 1 (P: .013 and .001, respectively). Total doses of ATG were higher in Group 1 patients (P: .007).

Conclusion: Despite the higher HLA-MM and RIS scores, clinical outcomes in desensitized patients were found to be similar to those in nondesensitized patients for acute rejection episodes and hospitalizations. Desensitization with rituximab in patients with high HLA-RIS scores can prevent acute rejection and hospitalization.
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http://dx.doi.org/10.1016/j.transproceed.2019.04.068DOI Listing
September 2019

Leukemia relapse following unmanipulated haploidentical transplantation: a risk factor analysis on behalf of the ALWP of the EBMT.

J Hematol Oncol 2019 07 4;12(1):68. Epub 2019 Jul 4.

Hematology and Bone Marrow Transplantation Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel.

Background: As information on incidence, risk factors, and outcome of acute leukemia (AL) relapse after unmanipulated haploidentical stem cell transplantation (haplo-SCT) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Methods: Among 1652 transplants performed for lymphoblastic and myeloid AL between 2007 and 2014, 587 patients (acute lymphoblastic leukemia (ALL) 131, acute myeloid leukemia (AML) 456) with detailed information were analyzed aiming to identify risk factors for post-transplant relapse and for overall survival (OS) after relapse.

Results: The cumulative incidence of relapse at 3 years was 44% (35-53%) for ALL and 32% (27-36%) for AML (p = 0.023). In ALL, risk factors for relapse were disease status different from the first complete remission (CR1) at haplo-SCT (CR2 vs CR1: HR 2.85, p = 0.011; advanced vs CR1: HR 14.28, p < 0.0001) and male donor gender (HR 3.64, p = 0.0002), while in AML, risk factors were advanced disease at haplo-SCT (advanced vs CR1: HR 3.95, p < 0.0001) and comorbidities (HCT-CI) ≥ 3 (HR 1.75, p = 0.014). Transplants performed in more recent years were associated with lower relapse incidence (RI) in AML, but not in ALL (HR 0.91, p = 0.042). After relapse, median follow-up was 13 months (mos). OS at 1-year post relapse was 18%. Prognostic factors for superior OS after relapse were remission at time of haplo-SCT (CR vs advanced: HR 0.71, p = 0.028), time from transplant to relapse (≥ 5 mos vs < 5 mos: HR 0.530, p < 0.0001), and bone marrow as a stem cell source (peripheral blood (PB) vs bone marrow (BM): HR 1.473, p = 0.016).

Conclusions: Risk factors for relapse after haploidentical transplantation were disease specific. Longer OS after relapse was achieved in particular by patients both in CR at haplo-SCT and relapsing more than 5 months after transplant (1-year OS 33%).
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http://dx.doi.org/10.1186/s13045-019-0751-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610936PMC
July 2019

Allogeneic Stem Cell Transplantation for Blast Crisis Chronic Myeloid Leukemia in the Era of Tyrosine Kinase Inhibitors: A Retrospective Study by the EBMT Chronic Malignancies Working Party.

Biol Blood Marrow Transplant 2019 10 1;25(10):2008-2016. Epub 2019 Jul 1.

Division of Hematology, Department of Oncology, University Hospital, Geneva, Switzerland; Faculty of Medicine of Geneva, University of Geneva, Geneva Switzerland.

The prognosis of patients with blast crisis (BC) chronic myeloid leukemia (CML) is still dismal. Allogeneic stem cell transplantation represents the only curative treatment option, but data on transplant outcomes are scarce. We therefore conducted a retrospective, registry-based study of adult patients allografted for BC CML, focusing on patients with active disease at transplant and pretransplant prognostic factors. One hundred seventy patients allografted for BC CML after tyrosine kinase inhibitor pretreatment between 2004 and 2016 were analyzed. Before transplant, 95 patients were in remission, whereas 75 patients had active BC. In multivariable analysis of the entire cohort, active BC at transplant was the strongest factor associated with decreased overall survival (hazrd ratio, 1.87; P = .010) and shorter leukemia-free survival (LFS; hazard ratio, 1.69; P = .017). For patients with BC in remission at transplant, advanced age (≥45 years), lower performance status (≤80%), longer interval from diagnosis BC to transplant (>12 months), myeloablative conditioning, and unrelated donor (UD) transplant were risk factors for inferior survival. In patients with active BC, only UD transplant was significantly associated with prolonged LFS and trended toward improved overall survival. In summary, survival of patients allografted for BC CML was strongly dependent on pretransplant remission status. In patients with remission of BC, conventional prognostic factors remained the major determinants of outcome, whereas in those with active BC at transplant, UD transplant was associated with prolonged LFS in our study.
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http://dx.doi.org/10.1016/j.bbmt.2019.06.028DOI Listing
October 2019

Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission.

Blood Adv 2019 06;3(12):1826-1836

Center for International Blood and Marrow Transplant Research, Department of Medicine, and.

HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy-based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival ( = .15), leukemia-free survival ( = .50), nonrelapse mortality ( = .16), relapse ( = .90), or grade II-IV acute GVHD ( = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; < .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease-donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy-based Haplo-HCT vs MSD using calcineurin inhibitor-based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.
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http://dx.doi.org/10.1182/bloodadvances.2019000050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595262PMC
June 2019

A familial Mediterranean fever patient with double homozygous mutations treated with anakinra after kidney transplantation.

Nefrologia 2020 Sep - Oct;40(5):563-564. Epub 2019 Jun 11.

Health Sciences University Medical Faculty, Department of Internal Medicine, Sisli Hamidiye Etfal Training and Research Hospital, Clinic of Nephrology, Turkey.

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http://dx.doi.org/10.1016/j.nefro.2019.03.012DOI Listing
June 2019

Hematopoietic stem cell transplantation with unrelated cord blood or haploidentical donor grafts in adult patients with secondary acute myeloid leukemia, a comparative study from Eurocord and the ALWP EBMT.

Bone Marrow Transplant 2019 12 31;54(12):1987-1994. Epub 2019 May 31.

Hôpital Saint Antoine, Service d'Hématologie et Thérapie Cellulaire, AP-HP, Paris, France.

Survival of patients with secondary acute myeloid leukemia (sAML) is poor. Cord blood transplantation (UCBT) and non-T-cell-depleted stem cell transplantation from haploidentical donors (HAPLO) are both strategies that have shown encouraging results in patients who do not have an human leukocyte antigen (HLA)-matched sibling or unrelated donor. We retrospectively analyzed outcomes of 409 adults with sAML receiving either UCBT (n = 163) or HAPLO (n = 246) in EBMT centers. Myelodysplastic syndrome (MDS) or myeloproliferative disorder (MPD) was the antecedent diagnosis in 79% of UCBT and 85% of HAPLO recipients. In multivariate analysis, UCBT was associated with higher risk of grade II-IV acute GVHD (HR 1.9, p = 0.009) and lower GHVD-free-relapse-free-survival (GRFS) (HR 1.57, p = 0.007) compared to HAPLO. Chronic-GVHD, RI, NRM, LFS, and OS were not statistically different between the two. Early disease stage at transplant was independently associated with lower RI and NRM and higher OS and LFS. These results indicate that HAPLO is associated with better GRFS and lower aGvHD compared to UCBT in patients with sAML and that UCBT can be a valid alternative for sAML patients who lack a matched sibling, a proper haploidentical or an unrelated donor.
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http://dx.doi.org/10.1038/s41409-019-0582-5DOI Listing
December 2019

Impact of conditioning intensity on outcomes of haploidentical stem cell transplantation for patients with acute myeloid leukemia 45 years of age and over.

Cancer 2019 05 8;125(9):1499-1506. Epub 2019 Jan 8.

ALWP Office, Saint-Antoine Hospital, Paris, France.

Background: T cell-replete haploidentical stem cell transplantation (haplo-SCT) is a valid therapeutic option for adult patients with high-risk acute myeloid leukemia (AML) lacking an HLA-matched sibling or unrelated donor.

Method: We retrospectively analyzed the outcomes of 912 AML patients ≥45 years of age who had undergone haplo-SCT with either myeloablative conditioning (MAC; n = 373) or reduced intensity conditioning (RIC; n = 539) regimens.

Results: The median follow-up was 31.1 and 25.7 months for MAC and RIC, respectively. The incidence of relapse and nonrelapse mortality (NRM) were 25.1% versus 28.7% and 31.0% versus 30.3% for MAC and RIC, respectively; 2-year leukemia-free survival (LFS) was 43.9% for MAC versus 41.0% for RIC. In multivariate analysis, the use of MAC versus RIC was not associated with a difference in the outcomes. Results were confirmed in the propensity score-weighted analysis. Disease status and performance status at transplantation were associated with outcomes. Notably, the use of posttransplantation cyclophosphamide was associated with reduced acute graft-versus-host disease (aGVHD) stage III-IV, and NRM and increased overall survival, LFS, and GVHD-free, relapse-free survival. The use of mobilized peripheral blood stem cells was associated with an increased risk of stage II-IV aGVHD.

Conclusion: No differences were found between MAC and RIC regimens for haplo-SCT in adults with AML who were ≥45 years of age. The type of GVHD prophylaxis, disease status, and performance status were the major predictors of transplantation outcome. These results may serve as the background for randomized study comparing RIC versus MAC for haplo-SCT in adults with AML.
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http://dx.doi.org/10.1002/cncr.31941DOI Listing
May 2019

Beneficial role of CD8+ T-cell reconstitution after HLA-haploidentical stem cell transplantation for high-risk acute leukaemias: results from a clinico-biological EBMT registry study mostly in the T-cell-depleted setting.

Bone Marrow Transplant 2019 06 7;54(6):867-876. Epub 2018 Dec 7.

Perugia General Hospital and University, Perugia, Italy.

HLA-haploidentical haematopoietic stem cell transplantation (haplo-HSCT) is increasingly offered to patients with high-risk acute leukaemia. Unfortunately, haplo-HSCT is followed by a delayed immunoreconstitution. The aim of this EBMT registry study was to explore the clinical impact of lymphocyte subset counts after haplo-HSCT. We considered 144 leukaemic patients transplanted in the period 2001-2012. Pre-transplantation clinical variables and differential immune-cell counts (CD3, CD4, CD8 T cells, NK and B cells) measured before day 100 were evaluated for their capacity to predict overall survival, relapse mortality or non-relapse mortality (NRM). Negative prognostic factors for overall survival were advanced disease state at transplantation, host age and CMV seropositivity. Higher CD3, CD4 and CD8 counts were associated with a better overall survival and a lower NRM. Strikingly, when tested in multivariable analysis, higher CD3 and CD8 counts were still significantly associated with a lower NRM. These results indicate that an accelerated T-cell reconstitution correlates with less transplantation mortality, likely due to the protective role of T cells against viral infections. This observation suggests that CD8+ T-cell counts should be investigated as surrogate biomarkers of outcome in prospective haplo-HSCT trials.
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http://dx.doi.org/10.1038/s41409-018-0351-xDOI Listing
June 2019

Family Mismatched Allogeneic Stem Cell Transplantation for Myelofibrosis: Report from the Chronic Malignancies Working Party of European Society for Blood and Marrow Transplantation.

Biol Blood Marrow Transplant 2019 03 5;25(3):522-528. Epub 2018 Nov 5.

Department of Stem Cell Transplantation, University Hospital Eppendorf, Hamburg, Germany.

This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34 cell dose was 4.8 × 10/kg (range, 1.7 to 22.9; n = 43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28days was 82% (range, 70% to 93%), at a median of 21days (range, 19 to 23). At 2years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1- and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1- and 2- year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19% (95% CI 7% to 31%). The 2-year nonrelapse mortality was 38% (95% CI 24% to 51%). This retrospective study of MF allo-SCT using family mismatched donors demonstrated feasibility of the approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression-free survival rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality need to be used, ideally in a multicenter prospective fashion.
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http://dx.doi.org/10.1016/j.bbmt.2018.10.017DOI Listing
March 2019

Outcomes of Haploidentical Transplantation in Patients with Relapsed Multiple Myeloma: An EBMT/CIBMTR Report.

Biol Blood Marrow Transplant 2019 02 20;25(2):335-342. Epub 2018 Sep 20.

Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.

Allogeneic hematopoietic cell transplantation (allo-HCT) using siblings and matched donors has the potential for long-term disease control in a subset of high-risk patients with multiple myeloma (MM); however, the data on using haploidentical donors in this disease are limited. We conducted a retrospective analysis to examine the outcomes of patients with MM who underwent haploidentical allo-HCT within European Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research centers. A total of 96 patients underwent haploidentical allo-HCT between 2008 and 2016. With a median follow-up of 24.0 months (range, 13.2 to 24.9 months), 97% (95% confidence interval [CI], 93% to 100%) of patients had neutrophil engraftment by day 28, and 75% (95% CI, 66% to 84%) achieved platelet recovery by day 60. Two-year progression-free survival (PFS) was 17% (95% CI, 8% to 26%), and overall survival (OS) was 48% (95% CI, 36% to 59%). At 2 years, the cumulative risk of relapse/progression was 56% (95% CI, 45% to 67%), and 1-year nonrelapse mortality (NRM) was 21% (95% CI, 13% to 29%). The incidences of acute graft-versus-host-disease (GVHD) grades II-IV by 100 days and chronic GVHD at 2 years were 39% (95% CI, 28% to 49%) and 46% (95% CI, 34% to 59%), respectively. On univariate analysis, use of post-transplantation cyclophosphamide (PT-Cy) (54% [95% CI, 41% to 68%] versus 25% [95% CI, 1% to 48%]; P =.009) and use of bone marrow as source of stem cells (72% [95% CI, 55% to 89%] versus 31% [95% CI, 17% to 46%]; P = .001) were associated with improved OS at 2 years. Disease status, patient sex, intensity of conditioning regimen, recipient/donor sex mismatch, and cytomegalovirus serostatus had no impact on OS, PFS, or NRM. Haploidentical transplantation is feasible for patients with multiply relapsed or high-risk MM, with an encouraging 2-year OS of 48% and an NRM of 21% at 1 year, supporting further investigation of haploidentical allo-HCT in suitable candidates with MM.
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http://dx.doi.org/10.1016/j.bbmt.2018.09.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339830PMC
February 2019