Publications by authors named "Jean-Henri Bourhis"

88 Publications

Scoring system for clinically significant CMV infection in seropositive recipients following allogenic hematopoietic cell transplant: an SFGM-TC study.

Bone Marrow Transplant 2020 Dec 18. Epub 2020 Dec 18.

Department of Hematology, Univ. Lille, CHU Lille, F-59000, Lille, France.

In order to identify cytomegalovirus (CMV)-seropositive patients who are at risk of developing CMV infection following first allogeneic hematopoietic cell transplantation (allo-HCT), we built up a scoring system based on patient/donor characteristics and transplantation modalities. To this end, 3690 consecutive patients were chronologically divided into a derivation cohort (2010-2012, n = 2180) and a validation cohort (2013-2014, n = 1490). Haploidentical donors were excluded. The incidence of first clinically significant CMV infection (CMV disease or CMV viremia leading to preemptive treatment) at 1, 3, and 6 months in the derivation cohort was 13.8%, 38.5%, and 39.6%, respectively. CMV-seropositive donor, unrelated donor (HLA matched 10/10 or HLA mismatched 9/10), myeloablative conditioning, total body irradiation, antithymocyte globulin, and mycophenolate mofetil significantly and independently affected the incidence of 3-month infection. These six factors were selected to build up the prognostic model. Four risk groups were defined: low, intermediate-low, intermediate-high, and high-risk categories, with a 3-month predicted incidence of first clinically significant CMV infection in the derivation cohort of 22.2%, 31.1%, 45.4%, and 56.9%, respectively. This score represents a framework for the evaluation of patients who are at risk of developing clinically significant CMV infection following allo-HCT. Prospective studies using this score may be of benefit in assessing the value of anti-CMV prophylaxis in well-defined patient cohorts.
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http://dx.doi.org/10.1038/s41409-020-01178-6DOI Listing
December 2020

Allogeneic HCT for adults with B-cell precursor acute lymphoblastic leukemia harboring IKZF1 gene mutations. A study by the Acute Leukemia Working Party of the EBMT.

Bone Marrow Transplant 2020 Nov 25. Epub 2020 Nov 25.

Department of Hematology, Hospital Saint Antoine, Paris, France.

The presence of IKZF1 gene mutations is associated with poor prognosis of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The goal of this retrospective study was to evaluate outcome of allogeneic hematopoietic cell transplantation (allo-HCT) in this population. Ninety-five patients transplanted in first (n = 75) or second (n = 20) complete remission (CR) from either HLA-matched sibling (n = 32), unrelated (n = 47) or haploidentical (n = 16) donor were included in the analysis. The probabilities of the overall survival (OS) and leukemia-free survival (LFS) at 2 years were 55% and 47%, respectively. Relapse incidence (RI) was 32% while non-relapse mortality (NRM), 21%. The incidence of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD was 34% and 30%, respectively. The probability of GVHD and relapse-free survival (GRFS) was 35%. In a multivariate analysis positive minimal residual disease (MRD) status was associated with decreased chance of LFS (HR = 3.15, p = 0.004) and OS (HR = 2.37, p = 0.049) as well as increased risk of relapse (HR = 5.87, p = 0.003). Disease stage (CR2 vs. CR1) affected all, LFS, OS, GRFS, RI, and NRM. Results of allo-HCT for patients with BCP-ALL and IKZF1 mutations are generally improving, however, individuals with detectable MRD have poor prognosis and require additional intervention prior to transplantation.
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http://dx.doi.org/10.1038/s41409-020-01139-zDOI Listing
November 2020

A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia.

Blood 2021 Jan;137(4):524-532

Université de Paris, Génomes, Biologie Cellulaire et Thérapeutique U944, INSERM, CNRS, Paris, France.

A multistage model instructed by a large dataset (knowledge bank [KB] algorithm) has recently been developed to improve outcome predictions and tailor therapeutic decisions, including hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML). We assessed the performance of the KB in guiding HSCT decisions in first complete remission (CR1) in 656 AML patients younger than 60 years from the ALFA-0702 trial (NCT00932412). KB predictions of overall survival (OS) were superior to those of European LeukemiaNet (ELN) 2017 risk stratification (C-index, 68.9 vs 63.0). Among patients reaching CR1, HSCT in CR1, as a time-dependent covariate, was detrimental in those with favorable ELN 2017 risk and those with negative NPM1 minimal residual disease (MRD; interaction tests, P = .01 and P = .02, respectively). Using KB simulations of survival at 5 years in a scenario without HSCT in CR1 (KB score), we identified, in a similar time-dependent analysis, a significant interaction between KB score and HSCT, with HSCT in CR1 being detrimental only in patients with a good prognosis based on KB simulations (KB score ≥40; interaction test, P = .01). We could finally integrate ELN 2017, NPM1 MRD, and KB scores to sort 545 CR1 patients into 278 (51.0%) HSCT candidates and 267 (49.0%) chemotherapy-only candidates. In both time-dependent and 6-month landmark analyses, HSCT significantly improved OS in HSCT candidates, whereas it significantly shortened OS in chemotherapy-only candidates. Integrating KB predictions with ELN 2017 and MRD may thus represent a promising approach to optimize HSCT timing in younger AML patients.
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http://dx.doi.org/10.1182/blood.2020005524DOI Listing
January 2021

Medication non-adherence after allogeneic hematopoietic cell transplantation in adult and pediatric recipients: a cross sectional study conducted by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy.

Fundam Clin Pharmacol 2020 Aug 2. Epub 2020 Aug 2.

Hematologie Adulte, CHU Lille, Lille, F 59000, France.

Medication non-adherence (NA) after allogeneic hematopoietic cell transplantation (allo-HCT) can lead to serious complications. This study assesses NA in French adult and pediatric recipients and identifies factors associated with NA. In accordance with the EMERGE and STROBE guidelines, a cross sectional multicentric survey was conducted. We used a self-reported questionnaire that was adapted to adults and pediatrics and that could provide a picture of all three phases of medication adherence: initiation, implementation, persistence. We enrolled 242 patients, 203 adults (mean age: 51 years old, 50.7% male) and 39 children (mean age: 9 years old, 56.4% female). Reported NA was estimated at about 75% in both populations, adults and pediatrics. In adults, the univariate analysis showed that patients less than 50 years old (P = 0.041), (i) treated with cyclosporine (P = 0.02), (ii) treated with valacyclovir/acyclovir (P = 0.016), and (iii) experiencing side effects (P = 0.009), were significantly more non-adherent. In multivariate analysis, only recipient age was significantly associated to NA (P = 0.05). The limited size of the pediatric population did not allow us to draw any statistical conclusion about this population. To the best of our knowledge, this is the first study in France on NA in allo-HCT recipients. Our results highlight the age factor as the only factor related to NA. Further studies are needed to confirm our observations and refine results in pediatric populations, currently most at risk of medication NA.
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http://dx.doi.org/10.1111/fcp.12593DOI Listing
August 2020

Imaging in Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome.

Biol Blood Marrow Transplant 2020 10 25;26(10):1770-1779. Epub 2020 Jun 25.

Department of Hematology, Institut Gustave Roussy, Villejuif, France.

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation. Early diagnosis and, subsequently, earlier intervention have been shown to be beneficial to clinical outcomes. Diagnostic criteria from the European Society for Blood and Marrow Transplantation include recommendations on the use of imaging for diagnosis. This review discusses evidence on the use of imaging in the management of VOD/SOS and how imaging biomarkers can contribute to earlier diagnosis/treatment.
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http://dx.doi.org/10.1016/j.bbmt.2020.06.016DOI Listing
October 2020

Combined G-CSF and Plerixafor enhance hematopoietic recovery of CD34 cells from poor mobilizer patients in NSG mice.

Exp Hematol 2020 06 22;86:15-20.e2. Epub 2020 May 22.

Hematology/Immunology Unit, Gustave Roussy Cancer Center, Villejuif Cedex, France.

Transplantable CD34 hematopoietic stem/progenitor cells (HSPCs) are currently isolated mainly from peripheral blood after mobilization with granulocyte colony-stimulating factor (G-CSF). These mobilized CD34 cells have the potential to generate all blood cell types. For autologous transplantation, the minimal number of mobilized CD34 cells is 2 × 10 CD34 cells/kg body weight. However, up to 30% of patients fail to mobilize enough peripheral CD34 cells after G-CSF treatment. To overcome this limitation, a combination of G-CSF and Plerixafor, a CXCR4 chemokine receptor inhibitor, is proposed to enhance CD34 cell mobilization in poor mobilizer patients. However, only limited data are available on quantification of the functional quality of such patients' mobilized hematopoietic stem cells. Here, for six poor mobilizer patients, a head-to-head comparison of their CD34 cells mobilized without versus with Plerixafor was performed to assess their properties with respect to the reconstitution of human hematopoiesis in vivo in immune-deficient mice. Our results indicate that mobilized CD34 cells recovered after the G-CSF + Plerixafor mobilization protocol have an enhanced intrinsic hematopoietic reconstitution potential compared with CD34 cells mobilized with G-CSF alone.
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http://dx.doi.org/10.1016/j.exphem.2020.05.006DOI Listing
June 2020

Cost and efficacy of peripheral stem cell mobilization strategies in multiple myeloma.

Bone Marrow Transplant 2020 12 23;55(12):2254-2260. Epub 2020 May 23.

Hematology and Inserm CIC 1402, CHU, Poitiers, France.

Mobilization of peripheral blood stem cells (PBSC) can be performed using plerixafor, which is expensive, or high-dose cyclophosphamide (HDCy). We hypothesized that the overall cost of mobilization with plerixafor might not be greater if the cost of complication management was considered. We performed a cost analysis of these two strategies. This multicentric observational study recruited patients with myeloma who underwent a first PBSC mobilization. We considered direct medical costs, including hospitalization, mobilization agents, apheresis, and supportive treatments. We included 111 patients, 54 and 57 in the HDCy and plerixafor groups, respectively. Cost of mobilization with HDCy was 5097 ± 2982€ vs. 10958 ± 1789€ for plerixafor (p < 0.0001). Cost of agents used was 1287 ± 779€ vs. 6552 ± 509€, respectively (p = 0.0009). The mean number of days of hospitalization was 2 and 2.1 days, respectively (p = 0.035). All patients achieved the minimum PBSC collection target (p = 1.0); however, ASCT was performed with HDCy in 67% patients and with plerixafor in 86% (p = 0.02). Plerixafor mobilization incurred a greater cost, mostly due to the greater cost of the drug. Hospitalization length in the two groups was similar in our series. Interestingly, plerixafor appeared to be a very effective and safe mobilizing approach translating into a greater ASCT success.
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http://dx.doi.org/10.1038/s41409-020-0940-3DOI Listing
December 2020

Added prognostic value of secondary AML-like gene mutations in ELN intermediate-risk older AML: ALFA-1200 study results.

Blood Adv 2020 05;4(9):1942-1949

Department of Hematology, Saint-Louis Institute for Research, Université de Paris, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.

In this study, we aimed to refine prognostication of older with acute myeloid leukemia (AML) after intensive chemotherapy. Five hundred and nine patients aged 60 years or older (median age, 68 years) were prospectively enrolled in the intensive Acute Leukemia French Association (ALFA)-1200 trial between 2012 and 2016, and 471 patient samples were submitted to multigene analysis. Mutations in any of 8 genes frequently altered in myelodysplastic syndromes (MDS), including ASXL1, SRSF2, STAG2, BCOR, U2AF1, EZH2, SF3B1, and ZRSR2, defined a secondary AML (sAML)-like disease, as reported. Of the samples analyzed, 48% included sAML-like gene mutations. These mutations were associated with a shorter event-free survival, both overall (hazard ratio, 1.46; 95% confidence interval, 1.19-1.79; P < .001) and within the European LeukemiaNet (ELN)-2017 intermediate-risk subgroup (hazard ratio, 1.52; 95% confidence interval, 1.01-2.28; P = .044), which excludes ASXL1-mutated cases by definition. We therefore included patients with intermediate-risk AML carrying sAML-like mutations in a single high-risk patients group together with adverse-risk patients with AML, whereas other intermediate-risk patients were included in a standard-risk group together with favorable-risk patients (high-risk/standard-risk patient ratio, 1.00). Using this 2-class risk assessment, we observed that transplantation prolonged overall survival from remission in patients with high-risk AML only, not in patients with standard-risk AML. Routine analysis of sAML-like gene mutations may thus improve the definition of high-risk older patients with AML, and better identify the half of older patients who clearly derive survival benefit from allogeneic transplantation in first remission. This trial was registered at www.clinicaltrials.gov as #NCT01966497.
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http://dx.doi.org/10.1182/bloodadvances.2019001349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218423PMC
May 2020

Impact of the type of anthracycline and of stem cell transplantation in younger patients with acute myeloid leukaemia: Long-term follow up of a phase III study.

Am J Hematol 2020 07 17;95(7):749-758. Epub 2020 Apr 17.

EORTC Headquarters, Brussels, Belgium.

We provide a long-term evaluation of patients enrolled in the EORTC/GIMEMA AML-10 trial which included a total of 2157 patients, 15-60 years old, randomized to receive either daunorubicin (DNR, 50 mg/m ), mitoxantrone (MXR, 12 mg/m ), or idarubicin (IDA, 10 mg/m ) in addition to standard-dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA-identical sibling donor; in all other cases, an autologous HSCT had to be administered. At an 11-year median follow-up, the 5-year, 10-year and 15-year overall survival (OS) rates were 33.2%, 30.1% and 28.0%, respectively. No significant difference between the three randomized groups regarding OS was observed (P = .38). In young patients, 15-45 years old, no treatment difference (P = .89) regarding OS was observed, while in patients 46-60 years old, MXR and IDA groups had a trend for a longer OS as compared to the DNR group (P = .029). Among younger patients without a favorable MRC cytogenetic risk subgroup who achieved a CR/CRi after induction chemotherapy, those with a HLA-identical sibling donor had higher 10-year and 15-year OS rates than those without. In older patients who reached CR/CRi, the long-term outcomes of those with or without a donor was similar. In conclusion, long-term outcomes of the study confirmed similar OS in the three randomized groups in the whole cohort of patients.
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http://dx.doi.org/10.1002/ajh.25795DOI Listing
July 2020

Donor Lymphocyte Infusions After Allogeneic Transplantation: A Single-Center Experience.

Clin Lymphoma Myeloma Leuk 2020 04 2;20(4):209-211. Epub 2020 Jan 2.

Gustave Roussy, Villejuif, France.

Allogeneic hematopoietic cell transplantation (AHCT) represents the only curative therapy for many hematological malignancies. The graft versus leukemia effect, driven by donor T cells, plays a major role in its curative potential. This effect is sometimes very evident when patients with acute myeloid leukemia and myelodysplasia relapse after AHCT and are treated with donor lymphocyte infusions (DLIs). We retrospectively reviewed the charts of 64 patients who received DLI between 2012 and 2017 in our center. The mean age of the patients was 59 years (range, 34-79). Fifty percent were male (n = 32). The mean follow-up time after AHCT was 50.17 months (range, 8-174). The indication for DLI were disease progression, mixed chimerism, minimal residual disease, and other etiologies in 43.8%, 40.7%, 14%, and 1.5% of patients, respectively. The most common diagnosis was acute leukemia, followed by multiple myeloma. Of all patients, 59.4% received a transplant from a related donor, 39% received a transplant from an unrelated donor, and 1.6% received a transplant from a haploidentical donor. Reduced-intensity conditioning AHCT was the most frequent regimen used (53%). DLI was given alone in 79.7% of patients. Prophylactic DLI was given at 30 days after transplantation in patients who received human leukocyte antigen (HLA)-matched related human stem cell transplantation (HSCT) or 45 to 60 days post-transplant in patients receiving haploidentical HSCT or HLA-matched unrelated HSCT. Patients were treated without graft versus host disease (GVHD) prophylaxis. The use of DLI after transplantation remains a feasible procedure with rates of response >60%. Moreover, DLIs are well tolerated with a GVHD rate <10% in our series. We can hypothesize that in our experience the efficacy of this strategy does not rely on the induction of GVHD.
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http://dx.doi.org/10.1016/j.clml.2019.11.019DOI Listing
April 2020

Stem cell transplantation from a haploidentical donor versus a genoidentical sister for adult male patients with acute myelogenous leukemia in first remission: A retrospective study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation.

Cancer 2020 03 27;126(5):1004-1015. Epub 2019 Nov 27.

Department of Hematology and Cell Therapy, Saint-Antoine Hospital, Paris, France.

Background: In adult patients with acute myeloid leukemia (AML), a matched sibling donor (MSD) is considered the first choice for an allogeneic transplantation. However, a female donor for a male recipient is a poor prognostic factor. The authors compared haploidentical (HAPLO) donors with female MSDs.

Methods: In total, 834 men underwent allogenic transplantation from a female MSD, and 232 men underwent allogenic transplantation from a HAPLO donor. Of these, 86% of HAPLO recipients and 3% of MSD recipients received graft-versus-host disease (GVHD) prophylaxis posttransplantation with high-dose cyclophosphamide. A significant qualitative interaction was observed between donor type and cytogenetics, Therefore, the analyses were stratified on cytogenetics.

Results: Of the men with intermediate-risk AML, 638 received transplantation from a female MSD, and 160 received transplantation from a HAPLO donor. In multivariate analysis, poor risk factors were a HAPLO donor versus an MSD for nonrelapse mortality (hazard ratio [HR], 1.7; P = .02) and patient age for nonrelapse mortality and overall survival (HR, 1.22 [P = .02] and 1.15 [P = .02], respectively). HAPLO transplantation resulted in less chronic GVHD (HR, 0.43; P < 10 ) but lower leukemia-free survival (HR, 1.7; P = .04). The GVHD/relapse-free survival (GRFS) was not different. Of the men with high-risk AML, 196 received transplantation from a female MSD, and 72 received transplantation from a HAPLO donor. By multivariate analysis, HAPLO recipients had a lower incidence of relapse (HR, 0.40; P = .004), better leukemia-free survival (HR, 0.46; P = .003), better overall survival (HR, 0.43; P = .003), and better GRFS (HR, 0.54; P = .006).

Conclusions: In men who have intermediate-risk AML, allogenic transplantation from a sister MSD or a HAPLO donor produces similar GRFS. However, in men who have high-risk AML, a HAPLO donor combined with prophylactic high-dose cyclophosphamide posttransplantation may be a better choice.
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http://dx.doi.org/10.1002/cncr.32629DOI Listing
March 2020

Conditioning-based outcomes after allogeneic transplantation for myeloma following a prior autologous transplant (1991-2012) on behalf of EBMT CMWP.

Eur J Haematol 2020 Mar 25;104(3):181-189. Epub 2019 Dec 25.

University Hospital Eppendorf, Hamburg, Germany.

Objectives: The aim of this study was to compare the effect of the intensity of conditioning approaches used in allogeneic transplantation in myeloma-reduced intensity conditioning (RIC), non-myeloablative (NMA), myeloablative conditioning (MAC) or Auto-AlloHCT-on outcomes in patients who had had a prior autologous transplant.

Methods: A retrospective analysis of the EBMT database (1991-2012) was performed.

Results: A total of 344 patients aged between 40 and 60 years at the time of alloHCT were identified: 169 RIC, 69 NMA, 65 MAC and 41 Auto-Allo transplants. At a median follow-up of 54 months, the probabilities of overall survival (OS) at 5 years were 39% (95% CI 31%-47%), 45% (95% CI 32%-57%), 19% (95% CI 6%-32%) and 34% (95% CI 17%-51%), respectively. Status at allogeneic HCT other than CR or PR conferred a 70% higher risk of death and a 40% higher risk of relapse. OS was markedly lower in the MAC group (P = .004). MAC alloHCT was associated with a higher risk of death than RIC alloHCT until 2002 (HR = 4.1, P < .001) but not after 2002 (HR = 1.2, P = .276).

Conclusion: From 1991 to 2002, MAC was associated with poorer OS. Between 2003 and 2012, there were no significant differences in outcomes based on these different approaches.
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http://dx.doi.org/10.1111/ejh.13352DOI Listing
March 2020

The impact of anti-thymocyte globulin on the outcomes of Patients with AML with or without measurable residual disease at the time of allogeneic hematopoietic cell transplantation.

Leukemia 2020 04 14;34(4):1144-1153. Epub 2019 Nov 14.

Service d'Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, AP-HP, Sorobonne University, and INSERM UMRs 938, Paris, France.

Measurable residual disease (MRD) status pre-allogeneic hematopoietic cell transplantation (allo-HCT) has been shown to predict transplant outcomes. We investigated the effect of Anti-Thymocyte Globulin (ATG) on acute myelogenous leukemia (AML) relapse by pretransplant MRD status. AML patients undergoing allo-HCT in first complete remission from either a matched sibling or unrelated donor during the 2006-2017 period were selected. Outcomes of 1509 patients (MRD, n = 426) were studied. ATG was used in 561 (52%) and 239 (58%) patients within the MRD and MRD cohorts, respectively. In MRD patients, ATG did not affect relapse incidence (RI) (HR = 0.80, p = 0.17), but was associated with reduced incidence of grade II-IV acute GVHD, grade II-IV and chronic GVHD, reduced nonrelapse mortality (HR = 0.66, p = 0.05), improved leukemia-free survival (HR = 0.74, p = 0.02), overall survival (HR = 0.69, p = 0.01), and GVHD-relapse free survival (HR = 0.62, p < 0.01). In MRD patients, ATG was associated with a lower incidence of chronic GVHD (total, HR 0.56 p = 0.03; extensive, HR 0.40 P = 0.01), without an impact on other allo-HCT outcome parameters, including RI(HR = 1.02, p = 0.92). The use of ATG was associated with reduced risk for GVHD. ATG did not increase RI, even in high-risk AML patients who were MRD before allo-HCT.
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http://dx.doi.org/10.1038/s41375-019-0631-5DOI Listing
April 2020

Influence of alternative donor type on early survival after hematopoietic stem cell transplantation for acute myeloid leukemia lacking a sibling donor.

Bone Marrow Transplant 2020 04 29;55(4):749-757. Epub 2019 Oct 29.

CHU (University Hospital) de Grenoble Alpes, Grenoble, France.

Allogeneic hematopoietic stem cell transplantation is the only potentially curative therapy for acute myeloid leukemia. In the absence of an HLA-matched related or unrelated donor (MRD or MUD), the best alternative donor source remains controversial. Umbilical cord blood and haploidentical donors offer a shorter delay from indication to transplantation. This retrospective multicentre study of a French registry compares overall survival in the 18 months following registration in the absence of a MRD between four types of donors. Between 2012 and 2016, 1302 patients were transplanted using MUD (control, n = 803), mismatched MUD (n = 219), umbilical cord blood (n = 153) and haploidentical (n = 127) donors. Multivariate analyses were conducted for overall survival after registration, after transplant, and transplant-related mortality. After adjustment for variables, the type of donor did not influence any of the three end points. Our results confirmed the significant negative impact of longer time between registration and transplant: HR = 1.04 [1.02-1.06] (p < 0.0001). This indicates a positive correlation between better survival and shorter registration-to-transplantation wait time. In the absence of a sibling donor, the alternative stem cell source does not impact early survival in acute myeloid leukemia patients. The minimization of registration-to-transplantation time should be considered when weighing the alternative donor options.
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http://dx.doi.org/10.1038/s41409-019-0722-yDOI Listing
April 2020

Allogeneic stem cell transplantation in second complete remission for core binding factor acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Haematologica 2020 Jun 22;105(6):1723-1730. Epub 2019 Aug 22.

EBMT Paris Study Office, Paris, France.

Core binding factor acute myeloid leukemia (AML) comprises two subtypes with distinct cytogenetic abnormalities of either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22). Since long-term response to chemotherapy in these leukemias is relatively good, allogeneic hematopoietic stem cell transplantation is considered in patients who relapse and achieve second complete remission. To evaluate the outcomes of allogeneic transplantation in this indication, we studied 631 patients reported to the European Society for Blood and Marrow Transplantation Registry between the years 2000 and 2014. Leukemia-free survival probabilities at two and five years were 59.1% and 54.1%, while overall survival probabilities were 65% and 58.2%, respectively. The incidence of relapse and risk of non-relapse mortality at the same time points were 19.8% and 22.5% for relapse and 20.9% and 23.3% for non-relapse mortality, respectively. The most important adverse factors influencing leukemia-free and overall survival were: leukemia with t(8;21), presence of three or more additional chromosomal abnormalities, and Karnofsky performance score <80. Relapse risk was increased in t(8;21) leukemia and associated with additional cytogenetic abnormalities as well as reduced intensity conditioning. Measurable residual disease in molecular evaluation before transplantation was associated with increased risk of relapse and inferior leukemia-free survival.
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http://dx.doi.org/10.3324/haematol.2019.222810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271580PMC
June 2020

Impact of antithymocyte globulin on outcomes of allogeneic hematopoietic cell transplantation with TBI.

Blood Adv 2019 07;3(13):1950-1960

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

The impact of the use of antithymocyte globulin (ATG) following a total body irradiation (TBI)-based myeloablative conditioning regimen has been poorly explored. We retrospectively analyzed 724 patients who underwent a first allogeneic hematopoietic cell transplantation (allo-HCT) following a TBI-based conditioning regimen for acute myeloid leukemia (AML) and compared the outcomes of 251 (35%) patients who received ATG (ATG group) with 473 (65%) patients who did not (non-ATG group). Median follow-up of surviving patients was 59 months (interquartile range, 28-83). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) for non-ATG and ATG groups in the first 100 days was 33% vs 24%, respectively ( = .0098). The 2-year cumulative incidence of chronic graft-versus-host disease (cGVHD) was reduced significantly in the ATG group in comparison with the non-ATG group (46% vs 34%, = .003). Using multivariate analysis, in vivo T-cell depletion (ATG group) was independently associated with a decreased incidence of grade II-IV aGVHD (hazard ratio [HR], 0.28; < .001), grade III-IV aGVHD (HR, 0.21; < .001), cGVHD (HR, 0.63; = .02), and nonrelapse mortality (NRM) (HR, 0.54; = .02). Relapse risk, overall survival, and leukemia-free survival were similar between the 2 groups. Our results suggest that the addition of ATG to TBI-based myeloablative conditioning for allo-HCT in AML patients results in a significant reduction in aGVHD and cGVHD, translating into a significant reduction in NRM without increasing the relapse rate.
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http://dx.doi.org/10.1182/bloodadvances.2019000030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616257PMC
July 2019

The prognostic impact of the cytomegalovirus serostatus in patients with chronic hematological malignancies after allogeneic hematopoietic stem cell transplantation: a report from the Infectious Diseases Working Party of EBMT.

Ann Hematol 2019 Jul 16;98(7):1755-1763. Epub 2019 Apr 16.

Collegium Medicum UMK, University Hospital, Bydgoszcz, Poland.

It has been shown recently that donor and/or recipient cytomegalovirus (CMV) seropositivity is associated with a significant overall survival (OS) decline in acute leukemia patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We now analyzed the prognostic impact of the donor/recipient CMV serostatus in 6968 patients with chronic hematological malignancies who underwent allo-HSCT. Donor and/or recipient CMV seropositivity was associated with a significantly reduced 2-year progression-free survival (PFS, 50% vs. 52%, p = 0.03) and OS (62% vs. 65%, p = 0.01). Multivariate Cox regression analyses showed an independent negative prognostic impact of donor and/or recipient CMV seropositivity on PFS (HR, 1.1; 95% CI, 1.0-1.2; p = 0.03), OS (HR, 1.1; 95% CI, 1.0-1.2; p = 0.003), and non-relapse mortality (HR, 1.2; 95% CI, 1.0-1.3; p = 0.02). OS decline was strongest for CMV-seropositive recipients with a CMV-seronegative donor (HR, 1.2; 95% CI, 1.1-1.3), followed by CMV-seropositive patients with a CMV-seropositive donor (HR, 1.1; 95% CI, 1.0-1.2). Conversely, OS did not differ significantly between CMV-seronegative recipients allografted from a CMV-seropositive donor (HR, 1.0; 95% CI, 0.9-1.2) and patients with donor/recipient CMV seronegativity (p = 0.001 for the four groups together). Non-relapse mortality was also significantly (p = 0.01) higher for CMV-seropositive patients with a CMV-seronegative graft (HR, 1.2; 95% CI, 1.1-1.4) than for CMV-seropositive patients with a CMV-seropositive graft (HR, 1.1; 95% CI, 0.9-1.2) or CMV-seronegative recipients with a CMV-seropositive graft (HR, 1.0; 95% CI, 0.8-1.2). Donor and/or recipient CMV seropositivity still results in an OS decline in patients with chronic hematological malignancies who have undergone allo-HSCT. However, this OS decline seems to be lower than that described for acute leukemia patients previously.
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http://dx.doi.org/10.1007/s00277-019-03669-zDOI Listing
July 2019

Comparison of Dynamic International Prognostic Scoring System and MYelofibrosis SECondary to PV and ET Prognostic Model for Prediction of Outcome in Polycythemia Vera and Essential Thrombocythemia Myelofibrosis after Allogeneic Stem Cell Transplantation.

Biol Blood Marrow Transplant 2019 06 28;25(6):e204-e208. Epub 2019 Mar 28.

University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address:

We aimed to validate the MYelofibrosis SECondary to PV and ET prognostic model (MYSEC-PM) in 159 patients with myelofibrosis secondary to polycythemia vera (PV) and essential thrombocythemia (ET) from the European Society for Blood and Marrow Transplantation registry undergoing transplantation from matched siblings or unrelated donors. Furthermore, we aimed to test its prognostic performance in comparison with the Dynamic International Prognostic Scoring System (DIPSS). Score performance was analyzed using the concordance index (C): the probability that a patient who experienced an event had a higher risk score than a patient who did not (C > .5 suggesting predictive ability). Median follow-up of the total cohort was 41 months (range, 34 to 54), 45 months in post-PV and 38 months in post-ET myelofibrosis. Survival at 1, 2, and 4 years was 70% (95% CI, 63% to 77%), 61% (95% CI, 53% to 69%), and 52% (95% CI, 43% to 61%) for the total cohort; 70% (95% CI, 59% to 80%), 61% (95% CI, 49% to 73%), and 51% (95% CI, 38% to 64%) for post-PV; and 71% (95% CI, 61% to 81%), 61% (95% CI, 50% to 72%), and 54% (95% CI, 42% to 66%) for post-ET myelofibrosis (P = .78). Overall, the DIPSS was not significantly predictive of outcome (P = .28). With respect to the MYSEC-PM, overall survival at 4 years was 69% for the low-risk, 55% for the intermediate 1-risk, 47% for the intermediate 2-risk, and 22% (0% to 45%) for the high-risk groups. The prognostic model was predictive of survival overall (P = .05), whereas groups with intermediate 2 and high risk showed no significant difference (P = .44). Assessment of prognostic utility yielded a C-index of .575 (95% CI, .502 to .648) for the DIPSS, whereas assessment of the MYSEC-PM resulted in a C-statistics of .636 (95% CI, .563 to .708), indicating improvement in prediction of post-transplant survival using the new MYSEC-PM. In addition, transplantations from an unrelated donor in comparison with an HLA-identical sibling showed worse outcome (P = .04), and transplant recipients seropositive for cytomegalovirus in comparison with seronegative recipients (P = .01) showed worse survival. In conclusion, incorporating transplant-specific and clinical and mutational information together with the MYSEC-PM may enhance risk stratification.
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http://dx.doi.org/10.1016/j.bbmt.2019.03.024DOI Listing
June 2019

Prognostic significance of recurring chromosomal abnormalities in transplanted patients with acute myeloid leukemia.

Leukemia 2019 08 7;33(8):1944-1952. Epub 2019 Mar 7.

Hematology Division, Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer, Israel.

Baseline cytogenetic studies at diagnosis remain the single most important determinant of outcome in patients with acute myeloid leukemia (AML). However, the prognostic role of the complete gamut of cytogenetic aberrations in AML patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently undefined. In addition, their significance in conjunction with FLT3-ITD status has not been addressed thus far. Using the ALWP/EBMT registry we conducted a retrospective analysis to determine the clinical outcomes of AML patients undergoing allo-HSCT with respect to specific recurring cytogenetic abnormalities complemented with FLT3-ITD status. We analyzed a cohort consisting of 8558 adult AML patients who underwent allo-HSCT from either a matched sibling or a matched unrelated donor. Patients with inv(3)(q21q26)/t(3;3)(q21;q26), del(5q), monosomy 7, chromosome 17p abnormalities, t(10;11)(p11-14;q13-23), t(6;11)(q27;q23), as well as those patients with a monosomal or complex karyotype experienced significantly inferior leukemia-free survival (LFS) compared to patients with a normal karyotype. Trisomy 14, del(9q), and loss of chromosome X were associated with improved LFS rates. A novel prognostic model delineating 5 distinct groups incorporating cytogenetic complexity and FLT3-ITD status was constructed with significant prognostic implications. Our analysis supports the added prognostic significance of FLT3-ITD to baseline cytogenetics in patients undergoing allo-HSCT.
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http://dx.doi.org/10.1038/s41375-019-0439-3DOI Listing
August 2019

Evaluation of infectious complications after haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide following reduced-intensity and myeloablative conditioning: a study on behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC).

Bone Marrow Transplant 2019 10 15;54(10):1586-1594. Epub 2019 Feb 15.

Institut de Cancérologie Lucien Neuwirth, Saint-Etienne, France.

Several approaches have been developed to overcome historical barriers associated with poor outcomes in the setting of HLA-haploidentical allogeneic transplantation (HaploSCT). Here, we examine the outcome of patients with various hematological disorders undergoing HaploSCT with high-dose, post-transplantation cyclophosphamide. We performed a retrospective study on 381 patients from 30 centers between January 2013 and December 2015. At the last follow-up, a total of 1058 infectious episodes were diagnosed, affecting 90.3% of the cohort. Median time to first infection was 13 days for bacterial, 32 days for viral and 20 days for fungal infections. Around 41% of these infections were of bacterial origin and 35% of viral origin, among which 48.8% of patients presented CMV reactivation. Median of GVHD relapse-free survival, progression-free survival and overall survival were 7.1 months, 19.9 months and 33.5 months, respectively. HSCT procedure was the primary or contributing cause of death (55.6%), followed by relapse of the original disease (34.2%). Infections accounted for 45.7% of the HSCT-related deaths. The present multicenter data on a large cohort of patients receiving HaploSCT with PTCy confirmed the feasibility of the procedure with an acceptable incidence of infectious complications, not different as compared to other haploidentical platforms or HLA-matched transplantation.
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http://dx.doi.org/10.1038/s41409-019-0475-7DOI Listing
October 2019

Antilymphocyte globulin for matched sibling donor transplantation in patients with myelofibrosis.

Haematologica 2019 06 17;104(6):1230-1236. Epub 2019 Jan 17.

EBMT Data Office Leiden, the Netherlands.

The use of antihuman T-lymphocyte immunoglobulin in the setting of transplantation from an HLA-matched related donor is still much debated. Acute and chronic graft--host disease are the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. The aim of this study was to evaluate the effect of antihuman T-lymphocyte immunoglobulin in a large cohort of patients with myelofibrosis (n=287). The cumulative incidences of grade II-IV acute graft--host disease among patients who were or were not given antihuman T-lymphocyte immunoglobulin were 26% and 41%, respectively. The corresponding incidences of chronic graft--host disease were 52% and 55%, respectively. Non-adjusted overall survival, disease-free survival and non-relapse mortality rates were 55% 53%, 49% 45%, and 32% 31%, respectively, among the patients who were or were not given antihuman T-lymphocyte immunoglobulin. An adjusted model confirmed that the risk of acute graft--host disease was lower following antihuman T-lymphocyte immunoglobulin (hazard ratio, 0.54; =0.010) while it did not decrease the risk of chronic graft--host disease. The hazard ratios for overall survival and non-relapse mortality were 0.66 and 0.64, with -values of 0.05 and 0.09, respectively. Antihuman T-lymphocyte immunoglobulin did not influence disease-free survival, graft--host disease, relapse-free survival or relapse risk. In conclusion, in the setting of matched related transplantation in myelofibrosis patients, this study demonstrates that antihuman T-lymphocyte immunoglobulin decreases the risk of acute graft--host disease without increasing the risk of relapse.
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http://dx.doi.org/10.3324/haematol.2018.201400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545844PMC
June 2019

Comparative outcomes of myeloablative and reduced-intensity conditioning allogeneic hematopoietic cell transplantation for therapy-related acute myeloid leukemia with prior solid tumor: A report from the acute leukemia working party of the European society for blood and bone marrow transplantation.

Am J Hematol 2019 04 10;94(4):431-438. Epub 2019 Jan 10.

EBMT Paris study office/CEREST-TC, Paris, France.

Therapy-related acute myeloid leukemia (t-AML) arises as a late complication following antecedent solid tumors or hematologic diseases and their associated treatments. There are limited data regarding risk factors and outcomes following allogeneic hematopoietic cell transplantation (HCT) for t-AML following a prior solid tumor, and furthermore, the impact of myeloablative (MAC) vs reduced-intensity conditioning (RIC) on survival is unknown. The acute leukemia working party (ALWP) of the European society for blood and bone marrow transplantation (EBMT) performed a large registry study that included 535 patients with t-AML and prior solid tumor who underwent first MAC or RIC allogeneic HCT from 2000-2016. The primary endpoints of the study were OS and LFS. Patients receiving RIC regimens had an increase in relapse incidence (hazard ratio [HR], 1.52; 95% confidence interval [CI] 1.02-2.26; P = 0.04), lower LFS (HR, 1.52; 95% CI 1.12-2.05, P = 0.007), and OS (HR, 1.51; CI 1.09-2.09; P = 0.012). There were no differences in NRM and GRFS. Importantly, LFS and OS were superior in patients receiving ablative regimens due to a decrease in relapse. As NRM continues to decline in the current era, it is conceivable that outcomes of HCT for t-AML with prior solid tumor may be improved by careful patient selection for myeloablative regimens.
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http://dx.doi.org/10.1002/ajh.25395DOI Listing
April 2019

Clofarabine/busulfan-based reduced intensity conditioning regimens provides very good survivals in acute myeloid leukemia patients in complete remission at transplant: a retrospective study on behalf of the SFGM-TC.

Oncotarget 2018 11 27;9(93):36603-36612. Epub 2018 Nov 27.

Department of Hematology, CHU Hôtel Dieu, Nantes, France.

Background: Clofarabine has been proved to have higher anti-leukemic myeloid activity compared to fludarabine, a drug extensively used as part of reduced intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT).

Results: Eighty-four patients were included. The majority of patients had acute myeloid leukemia (AML, = 63). Sixty-one patients were in complete remission (AML = 55). With a median follow up of 31 months (range: 5.7-74.1), 2-year overall (OS) and disease-free (DFS) survivals, relapse incidence (RI), non-relapse mortality (NRM) and graft-versus-host disease (GVHD)/relapse free survival (GRFS) were 64.5% (53.8-75.2); 57.2% (46.2-68.2); 27.7% (18.2-37.9); 15.1% (8.2-23.9) and 43.6% (32.5-54.7), respectively. Considering AML in remission, 2-year OS, DFS, RI, NRM and GRFS were 74.2% (62-86.5); 66.8% (53.6-79.9); 23.4% (12.7-36); 9.8% (3.5-19.9) and 50.9% (36.9-64.9), respectively. Two-year outcomes were similar between CloB2A1 and CloB2A2 sub-groups. In multivariate analysis, active disease at transplant was the only factor adversely impacting 2 years outcomes.

Conclusions: CloB2A2/A1 RIC regimen provides very good results for AML patients allografted in CR and could be retained as a new RIC platform for these patients.

Materials And Methods: This was a retrospective study including all patients who received a clofarabine/busulfan based RIC allo-SCT for myeloid malignancies and reported within the SFGM-TC registry. RIC regimen consisted of clofarabine 30 mg/m/day 4 to 5 days (Clo), busulfan 3.2 mg/kg/day 2 days (B2) and 2.5 mg/kg/day of rabbit anti-thymocyte globulin 1 or 2 days (A1 or A2). The primary objective of the study was to report the main outcomes of the whole cohort at 2 years.
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http://dx.doi.org/10.18632/oncotarget.26391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290956PMC
November 2018

Scoring System Based on Post-Transplant Complications in Patients after Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome: A Study from the SFGM-TC.

Curr Res Transl Med 2019 02 8;67(1):8-15. Epub 2018 Sep 8.

CHU de Lille, LIRIC, INSERM U995, Université de Lille, 59000 Lille, France. Electronic address:

Purpose: We developed a prognostic scoring system to evaluate the prognosis of myelodysplastic syndrome (MDS) patients surviving more than 100 days allogeneic hematopoietic cell transplantation after (allo-HCT).

Patients And Methods: We performed a landmark analysis on a derivation cohort of 393 cases to identify prognostic factors for 3-year overall survival. Potential predictor variables included demographic and clinical data, transplantation modalities and early post-transplant complications. The scoring system was tested against a validation cohort which included 391 patients.

Results: Complications occurring before day 100 such as relapse [HR = 6.7; 95%CI, 4.5-10.0] (4 points), lack of platelet recovery [HR, 3.6; 95%CI, 2.2-5.8] (2 points), grade-II acute GVHD [HR = 1.7; 95%CI, 1.2-2.5] (1 point) and grade-III/IV [HR = 2.6; 95%CI, 1.8 -3.8] (2 points) were the only independent predictors of 3-year OS. The 3-year OS associated with low (0), intermediate (1-3) and high (≥4) risk scores was respectively 70%, 46% and 6%. The model performed consistently in both cohorts, with good calibration.

Conclusion: This post-transplant scoring system is a powerful predictor of outcome after allo-HCT for MDS, and can provide useful guidance for clinicians. Additional studies are required to evaluate this scoring system for other hematologic malignancies.
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http://dx.doi.org/10.1016/j.retram.2018.08.003DOI Listing
February 2019

High-dose therapy and autologous stem cell transplantation in marginal zone lymphomas: a retrospective study by the EBMT Lymphoma Working Party and FIL-GITMO.

Br J Haematol 2018 09 9;182(6):807-815. Epub 2018 Jul 9.

Ospedale degli Infermi, Biella, Italy.

The role of autologous stem cell transplantation (ASCT) in patients with marginal zone lymphoma (MZL) is debatable. This study investigated the outcome and prognostic factors affecting the outcome of patients undergoing ASCT for MZL. Eligible patients had non-transformed nodal, extra-nodal (MALT) or splenic MZL (SMZL), aged ≥18 years, who underwent a first ASCT between1994 and 2013 and were reported to the European Society for Blood and Marrow Transplantation, Fondazione Italiana Linfomi or Gruppo Italiano Trapianto Di Midollo Osseo registries. The study included 199 patients, [111 MALT lymphoma, 55 nodal MZL (NMZL) and 33 SMZL]. Median age at transplantation was 56 years. The median number of prior therapies was 2 (range 1-8), including rituximab in 71%. 95% had chemosensitive disease. 89% received a chemotherapy-based high-dose regimen. There were no significant differences in patient and transplant characteristics between the 3 histological subtypes except for a lower percentage of patients previously treated with rituximab in the MALT sub-group and more transplants performed in recent years in the other sub-groups. After a median follow-up of 5 years, 5-year cumulative incidence of relapse/progression and non-relapse mortality were 38% and 9%, respectively. Five-year event-free survival (EFS) and overall survival (OS) were 53% and 73%, respectively. Five-year cumulative incidence of second malignancies was 6%. Multivariate analysis revealed age ≥65 years was associated with a shorter EFS and OS. In addition, patients with SMZL had a shorter OS than those with MALT. ASCT may provide clinical benefit in MZL patients who have failed multiple lines of chemoimmunotherapy.
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http://dx.doi.org/10.1111/bjh.15454DOI Listing
September 2018

Measurable residual disease, conditioning regimen intensity, and age predict outcome of allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first remission: A registry analysis of 2292 patients by the Acute Leukemia Working Party European Society of Blood and Marrow Transplantation.

Am J Hematol 2018 09 15;93(9):1142-1152. Epub 2018 Aug 15.

Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer, Israel.

Patients with acute myeloid leukemia (AML) in morphological first complete remission (CR1) pre-allogeneic hematopoietic cell transplantation (HCT) may have measurable residual disease (MRD) by molecular and immunophenotyping criteria. We assessed interactions of MRD status with HCT conditioning regimen intensity in patients aged <50 years (y) or ≥50y. This was a retrospective study by the European Society for Blood and Marrow Transplantation registry. Patients were >18y with AML CR1 MRD NEG/POS and recipients of HCT in 2000-2015. Conditioning regimens were myeloablative (MAC), reduced intensity (RIC) or non-myeloablative (NMA). Outcomes included leukemia free survival (LFS), overall survival (OS), relapse incidence (RI), non-relapse mortality (NRM), chronic graft-vs-host (cGVHD), and GVHD-free and relapse-free survival (GRFS). The 2292 eligible patients were categorized into four paired groups: <50y MRD POS MAC (N = 240) vs RIC/NMA (N = 58); <50y MRD NEG MAC (N = 665) vs RIC/NMA (N = 195); ≥50y MRD POS MAC (N = 126) vs RIC/NMA (N = 230), and ≥50y MRD NEG MAC (N = 223) vs RIC/NMA (N = 555). In multivariate analysis RIC/NMA was only inferior to MAC for patients in the <50y MRD POS group, with worse RI (HR 1.71) and LFS (HR 1.554). Patients <50Y MRD NEG had less cGVHD after RIC/NMA HCT (HR 0.714). GRFS was not significantly affected by conditioning intensity in any group. Patients aged <50y with AML CR1 MRD POS status should preferentially be offered MAC allo-HCT. Prospective studies are needed to address whether patients with AML CR1 MRD NEG may be spared the toxicity of MAC regimens. New approaches are needed for ≥50y AML CR1 MRD POS.
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http://dx.doi.org/10.1002/ajh.25211DOI Listing
September 2018

Related donor transplants: has posttransplantation cyclophosphamide nullified the detrimental effect of HLA mismatch?

Blood Adv 2018 06;2(11):1180-1186

Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer Ramat-Gan, Israel.

We sought to identify whether posttransplantation cyclophosphamide (PT-Cy) reduces or eliminates the detrimental impact of HLA mismatching on outcomes of HLA-haploidentical related donor transplantation for acute leukemia. Data from 2143 donor-recipient pairs (n = 218 haploidentical sibling; n = 218 offspring; n = 1707 HLA-matched sibling) with acute myeloid or lymphoblastic leukemia were studied. All received a calcineurin inhibitor for graft-versus-host disease (GVHD) prophylaxis while high-dose PT-Cy was also given to recipients of haploidentical transplant. Patient age correlated with donor-recipient relationship: haploidentical siblings donated to patients aged 18 to 54 years whereas offspring donated to patients aged 55 to 76 years. Therefore, transplant outcomes were examined separately in the 2 patient age groups. In patients aged 18 to 54 years, there were no significant differences in outcomes except chronic GVHD, which was lower after haploidentical sibling compared to HLA-matched sibling transplant (hazard ratio [HR], 0.63; < .001). In patients aged 55 to 76 years, despite lower chronic GVHD (HR, 0.42; < .001), graft failure (14% vs 6%; = .003), nonrelapse mortality (HR, 1.48; = .02), and overall mortality (HR, 1.32; = .003) were higher after transplant from offspring compared with an HLA-matched sibling. These data demonstrate a superior outcome in older recipients when using an HLA-matched sibling instead of offspring, although there were differences in transplant platforms (GVHD prophylaxis and graft type) between the 2 groups. Validation of these findings requires a prospective randomized trial wherein the transplant platforms can be closely matched.
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http://dx.doi.org/10.1182/bloodadvances.2018018291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998932PMC
June 2018