Publications by authors named "Monzr M Al Malki"

50 Publications

Chronic Graft-Versus-Host Disease, Non-Relapse Mortality and Disease Relapse in Older versus Younger Adults Undergoing Matched Allogeneic Peripheral Blood Hematopoietic Cell Transplantation: A CIBMTR Analysis.

Transplant Cell Ther 2021 Oct 9. Epub 2021 Oct 9.

CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI; Fred Hutchinson Cancer Research Center, Seattle, WA.

Background: The effect of chronic graft-versus-host disease (cGVHD) on the risk of non-relapse mortality (NRM) and relapse has not been specifically studied in older adults, who are increasingly undergoing allogeneic hematopoietic cell transplantation (alloHCT) and surviving long-term to develop cGVHD. In this Center for International Blood and Marrow Transplant Research analysis, we tested our hypothesis that the risk of NRM was higher with the development of cGVHD, particularly among older adults (≥60 years).

Methods: We included 4429 adults ≥40 years who received first HLA-matched peripheral blood alloHCT for acute myeloid leukemia or myelodysplastic syndrome between the years 2008-2017. We compared outcomes of 4 groups: older adults (≥60 years) and younger adults (40-59 years) with or without cGVHD to determine the effect of older age and cGVHD on various outcomes. We used Cox proportional hazard models to determine the risk of NRM, relapse and overall survival (OS). We treated cGVHD as a time-dependent covariate. Severity of cGVHD was based on the CIBMTR clinical definitions.

Results: cGVHD was significantly associated with a higher risk of NRM and lower risk of relapse regardless of age. The risk of NRM was higher among older versus younger adults. Adults who developed cGVHD as a group had longer OS, compared to age-matched cohorts without cGVHD. Older adults had worse OS regardless of cGVHD. Among adults with cGVHD, clinically moderate or severe cGVHD was associated with a significantly higher risk of NRM and lower risk of relapse; severe cGVHD was associated with shorter OS, whereas mild and moderate cGVHD were associated with longer OS.

Conclusions: Among both younger and older adults, the development of cGVHD was associated with a higher risk of NRM, lower risk of relapse and longer OS. Older adults had a higher risk of NRM but the increased risk of NRM associated with cGVHD did not differ based on age. Development of mild-moderate cGVHD offered the most favorable balance between minimizing NRM and decreasing relapses. The relapse risk was lowest for adults with severe cGVHD, but high NRM resulted in shorter OS. Developing strategies to avoid clinically severe cGVHD is critically important.
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http://dx.doi.org/10.1016/j.jtct.2021.10.002DOI Listing
October 2021

Extramedullary disease relapse and progression after blinatumomab therapy for treatment of acute lymphoblastic leukemia.

Cancer 2021 Oct 11. Epub 2021 Oct 11.

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California.

Background: Blinatumomab has demonstrated encouraging activity in relapsed/refractory (r/r) and minimal residual disease-positive (MRD+) acute lymphoblastic leukemia (ALL). Extramedullary disease (EMD) relapse or relapse with CD19- disease has been observed after blinatumomab therapy in patients with r/r or MRD+ ALL. However, the pathophysiology and risk factors of treatment failure are not fully understood.

Methods: This study retrospectively reviewed the outcomes of adult patients with B-cell ALL treated with blinatumomab (n = 132) for either r/r (n = 103) or MRD+ disease (n = 29) at the authors' center (2013-2021) and analyzed factors associated with treatment response and EMD failure.

Results: The overall response rate was 64%. A lower marrow blast burden before blinatumomab (P = .049) and no history of previous EMD (P = .019) were significantly associated with a higher response. Among the patients who responded to blinatumomab, 56% underwent consolidation with allogeneic transplantation. Blinatumomab failure was observed in 89 patients; 43% of these patients (n = 38) either progressed or relapsed at extramedullary sites. A history of extramedullary involvement (53% vs 24%; P = .005) and retention of CD19 expression at the time of relapse/progression (97% vs 74%; P = .012) were associated with a higher risk for extramedullary failure. Central nervous system (CNS) failure after blinatumomab was encountered in 39% of the patients with EMD.

Conclusions: A history of EMD predicted an inferior response to blinatumomab therapy with a higher risk for relapse/progression at extramedullary sites (particularly CNS). Consolidation with allogenic transplantation in patients who primarily responded to blinatumomab did not abrogate the risk of extramedullary relapse. The incorporation of extramedullary assessment and the intensification of CNS prophylaxis may help in addressing extramedullary failure.

Lay Summary: Extramedullary failure is common during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia. A history of extramedullary disease predicts an inferior response to blinatumomab therapy and a higher risk for relapse/progression at extramedullary sites. Most extramedullary failure cases retain CD19 expression.
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http://dx.doi.org/10.1002/cncr.33967DOI Listing
October 2021

Treatment of allosensitized patients receiving allogeneic transplantation.

Blood Adv 2021 Oct;5(20):4031-4043

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX; and.

Donor-specific anti-HLA antibodies (DSAs) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these patients, who often have no other donor options and/or are in need to proceed urgently to transplantation. We studied a multimodality treatment with alternate-day plasma exchange (PE), rituximab, intravenous γ globulin (IVIg) and an irradiated donor buffy coat for patients with DSAs at 2 institutions. Thirty-seven patients with a median age of 51 years were treated with this desensitization protocol. Treatment outcomes were compared with a control group of HaploSCT patients without DSAs (n = 345). The majority of patients in the DSA group were female (83.8% vs 37.1% in controls, P < .001) and received stem cells from a child as the donor (67.6% vs 44.1%, P = .002). Mean DSA level before and after desensitization was 10 198 and 5937 mean fluorescence intensity (MFI), respectively, with mean differences of 4030 MFI. Fourteen of 30 tested patients (46.7%) had C1q positivity, while 8 of 29 tested patients (27.6%) remained positive after desensitization. In multivariable analysis, patients with initial DSA > 20 000 MFI and persistent positive C1q after desensitization had a significantly lower engraftment rate, which resulted in significantly higher non-relapse mortality and worse overall survival (OS) than controls, whereas graft outcome and survival of patients with initial DSA < 20 000 MFI and those with negative C1q after treatment were comparable with controls. In conclusion, treatment with PE, rituximab, IVIg, and donor buffy coat is effective in promoting engraftment in patients with DSAs ≤20 000 MFI.
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http://dx.doi.org/10.1182/bloodadvances.2021004862DOI Listing
October 2021

Safety and Tolerability of SARS-CoV2 Emergency-Use Authorized Vaccines for Allogeneic Hematopoietic Stem Cell Transplant Recipients.

Transplant Cell Ther 2021 Jul 15. Epub 2021 Jul 15.

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.

The safety and efficacy of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) emergency-use authorized (EUA) vaccines have been confirmed in the general population. However, there are no data on its safety and tolerability or efficacy in recipients of allogeneic hematopoietic stem cell transplant (HCT). We performed this study to identify the incidence of adverse events following SARS-CoV2 EUA vaccines, the incidence of new-onset graft-versus-host disease (GVHD) or worsening of existing GVHD after EUA vaccine administration, and the incidence SARS-CoV2 positivity in vaccinated HCT patients. We retrospectively reviewed 113 HCT patients who received at least one dose of EUA vaccine to describe the safety and tolerability, any impact on GVHD, and the incidence of SARS-CoV2 PCR positivity after vaccination. Patients received either Pfizer (BNT162b2) or Moderna (mRNA-1273) vaccines. Patients were included if they were 18 years or older and had received at least one dose of vaccine in the post-HCT setting. Most patients presented with myalgias/arthralgias (first dose, 7.7%; second dose, 14.6%), fatigue (first dose, 15.4%; second dose, 29.2%), and injection site pain (first dose, 40.4%; second dose, 43.8%). Other side-effects experienced by patients included nausea, vomiting, diarrhea, headache, and injection-site rash and swelling. Liver function abnormalities occurred in 18.6% of patients. Neutropenia, thrombocytopenia, and lymphopenia occurred in 13.3%, 11.5%, and 8.8% of patients, respectively. Forty percent of patients had active chronic GVHD at the time of vaccination, and worsening chronic GVHD occurred in 3.5% of the patients. New chronic GVHD developed in 9.7% of patients after vaccination. The SARS-CoV2 EUA vaccines were well tolerated in allogeneic HCT recipients.
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http://dx.doi.org/10.1016/j.jtct.2021.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280601PMC
July 2021

Posttransplant cyclophosphamide as GVHD prophylaxis for peripheral blood stem cell HLA-mismatched unrelated donor transplant.

Blood Adv 2021 06;5(12):2650-2659

Department of Hematology and HCT.

Efficacy of PTCy after mismatched unrelated donor (MMUD) HCT is unknown. In this pilot clinical trial, we enrolled 38 patients with hematologic malignancies scheduled to undergo MMUD-HCT (≥6/8 HLA-matched donors) onto 1 of 2 conditioning strata: myeloablative using fludarabine and fractionated total body irradiation (n = 19) or reduced intensity with fludarabine/melphalan (n = 19). Graft source was peripheral blood stem cells (PBSCs), and GVHD prophylaxis was PTCy, tacrolimus, and mycophenolate mofetil. Patients' median age was 53 years (range, 21-72 years). Median number of HLA mismatches was 2 (range, 1-4) of 12 loci. Twenty-three patients (61%) were considered racial (n = 12) or ethnic (n = 11) minorities. Median time to neutrophil engraftment was 16 days (range, 13-35 days). With a median follow-up of 18.3 months (range, 4.3-25.0 months) for surviving patients, 1-year overall survival (OS) and GVHD-free/relapse-free survival (GRFS) were 87% (95% confidence interval [CI]: 71-94) and 68% (95% CI: 51-81), respectively. Cumulative incidence of nonrelapse mortality at 100 days and 1 year were 0% and 11% (95% CI: 4-27), respectively, whereas relapse/progression was 11% (95% CI: 4-27). Cumulative incidence of 100-day acute GVHD grades 2-4 and 3-4 and 1-year chronic GVHD were 50% (95% CI: 36-69), 18% (95% CI: 9-36), and 48% (95% CI: 34-68), respectively. The rate of moderate/severe chronic GVHD was 3% in the entire cohort. We showed highly promising OS/GRFS rates with an acceptable risk profile after PBSC-MMUD-HCT with PTCy. This trial was registered at www.clinicaltrials.gov as #NCT03128359.
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http://dx.doi.org/10.1182/bloodadvances.2021004192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270662PMC
June 2021

Use of high-dose mesna and hyperhydration leads to lower incidence of hemorrhagic cystitis after posttransplant cyclophosphamide-based allogeneic transplantation.

Bone Marrow Transplant 2021 10 9;56(10):2464-2470. Epub 2021 Jun 9.

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.

Currently, there is no consensus on best practices to prevent hemorrhagic cystitis (HC) in patients receiving posttransplant cyclophosphamide (PTCy). We retrospectively reviewed 194 patients undergoing their first hematopoietic cell transplant (HCT) who received PTCy from 2014 to 2018 to describe the incidence and severity of HC, identify potential risk factors, and impact of HC on HCT outcomes. Standard HC prophylaxis was hyperhydration with forced diuresis and mesna at 320% the daily dose of PTCy. Incidence of HC was 31.4% at day +100 of HCT. Median onset of HC was 12 days with 11.5% grade 3 HC and no Grade 4 HC. Patients with chemical HC experienced earlier onset (7 days vs. 34 days, p < 0.001) with a shorter median resolution time (5 days vs. 14 days, p = 0.001) when compared to BK-associated HC. In multivariate analysis, age above 60 years (HR 4.16, p = 0.006) and myeloablative conditioning (HR 2.44, p = 0.054) were associated with higher risk for HC, but overall, HC did not affect nonrelapse mortality or overall survival. In conclusion, hyperhydration with forced diuresis combined with aggressive mesna dosing is an effective strategy in preventing severe PTCy-associated HC, subsequently preventing any negative impact on transplant outcome.
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http://dx.doi.org/10.1038/s41409-021-01364-0DOI Listing
October 2021

Allogeneic Hematopoietic Cell Transplantation for Relapsed and Refractory Philadelphia Negative B Cell ALL in the Era of Novel Salvage Therapies.

Transplant Cell Ther 2021 03 22;27(3):255.e1-255.e9. Epub 2020 Dec 22.

Gehr Family Center for Leukemia Research, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California.

Introduction of novel salvage therapies and expansion of the donor pool within the past decade have allowed more patients with relapsed/refractory (r/r) B cell acute lymphoblastic leukemia (B-ALL) to receive allogeneic hematopoietic cell transplantation (alloHCT). The impact of each salvage therapy on transplant outcomes have not been compared. Our primary objective was to determine post-HCT relapse-free survival (RFS) in adult patients with r/r Philadelphia-chromosome negative (Ph) B-ALL. We retrospectively studied alloHCT outcomes in 108 adult patients with r/r Ph B-ALL transplanted in morphological remission achieved by salvage therapy. Salvage therapies were chemotherapy-based combination (n = 45, 42%), blinatumomab (n=43, 40%), inotuzumab (n = 14, 13%), or CAR T cells (n = 6, 6%). The 2-year RFS and overall survival (OS) were 44% and 50%, respectively. In multivariable analysis, conditioning with reduced-intensity or non-myeloablative regimens (hazard ratio [HR] = 2.23, 95% confidence interval [CI], 1.31-3.80; P = .003), having received ≥3 lines of therapies prior to transplant (HR = 2.66, 95% CI, 1.56-4.54; P < .001), and inotuzumab (HR = 2.42, 95% CI, 1.14-5.12; Wald P value = .021) were independently associated with lower RFS. Blinatumomab (HR = 1.10, 95% CI, 0.62-1.96) had comparable RFS to chemotherapy. Incidence of hepatic sinusoidal syndrome was highest with inotuzumab (P < .001); however, 30-day mortality and intensive care unit admissions were not different per salvage therapy. The alloHCT in r/r Ph B-ALL after remission induction with blinatumomab or chemotherapy led to encouraging outcomes if morphologic CR was achieved. In contrast, pretransplantation inotuzumab therapy was associated with inferior RFS. Larger studies are warranted to confirm our observations. Early transplantation after relapse and the utilization of myeloablative conditioning, when feasible, were key factors associated with improved outcomes after alloHCT in these patients.
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http://dx.doi.org/10.1016/j.jtct.2020.12.020DOI Listing
March 2021

Red blood cell and platelet transfusion support in the first 30 and 100 days after allogeneic hematopoietic cell transplant.

Transfusion 2020 10 3;60(10):2225-2242. Epub 2020 Aug 3.

Division of Transfusion Medicine, Department of Pathology, City of Hope National Medical Center, Duarte, California, USA.

Background: Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients often require substantial but variable transfusion support.

Study Design And Methods: This single-center, retrospective study evaluated the red blood cell (RBC) and platelet (PLT) transfusion data of first-time allo-HSCT recipients transplanted in 2011 to 2017. Multivariate analyses were performed to assess the associations between patient and transplant-related factors and transfusion requirements.

Results: The study included 1762 patients who received peripheral blood stem cells (88.2%), marrow (7.0%), or umbilical cord (4.8%) from matched related (38.3%), unrelated (49.2%), or haploidentical (7.8%) donors. Almost all patients required RBCs (88.3%) or PLTs (97.4%) during the first 30 days, with medians of 3 (range, 1-37) RBC and 6 (range, 1-144) PLT units transfused. Fewer patients required RBC (43.8%) or PLT (27.3%) transfusions during Days 31 to 100, but the median (range) numbers of RBC and PLT units remained high at 3 (1-36) and 6 (1-116) among transfused patients. RBC and PLT transfusion independence was reached in medians of 24 (95% confidence interval [CI], 22-26) and 12 (95% CI, 11-12) days, respectively. Haploidentical donor, cord graft, and requiring RBC transfusions in the 10 days before HSCT were the most significant independent factors predictive of increased transfusion requirements. Advanced disease, diagnosis, ABO incompatibility, conditioning intensity, CD34+ cell dose, presence of severe acute graft-vs-host disease, and changes in recommended transfusion triggers were also shown to independently impact transfusion requirements.

Conclusions: This study provided for the first time quantitative and comparative transfusion data on a large contemporary cohort of HSCT recipients, including haploidentical and cord graft recipients, and identified factors predictive of increased transfusions.
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http://dx.doi.org/10.1111/trf.15961DOI Listing
October 2020

Venetoclax and hypomethylating agents in FLT3-mutated acute myeloid leukemia.

Am J Hematol 2020 Jul 6. Epub 2020 Jul 6.

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Gehr Family Center for Leukemia Research, Duarte, California, USA.

FMS-like tyrosine kinase 3 (FLT3) mutations are prevalent in acute myeloid leukemia (AML), and their presence confers adverse risk. FLT3-mutated (FLT3m) AML is a challenging leukemia to manage, particularly in older and unfit patients as well as patients with relapsed/refractory (r/r) disease. We retrospectively analyzed the outcomes of 50 FLT3m AML patients (17 treatment-naïve, 33 r/r) treated with venetoclax (VEN) and hypomethylating agents (HMA). The overall CR/CRi rate with VEN-HMA was 60% (94% in treatment-naïve AML and 42% in r/r AML). Early (60-days) treatment related mortality was 2%. The r/r AML setting was an independent predictor of lower complete response (OR: 0.08; 95%CI: 0.00-0.60, P = .03). Cytogenetics-molecular risk, concurrent mutations, the type of FLT3 mutation (ITD vs TKD), the ITD allelic ratio, the type of HMA, age, prior exposure to HMA and receipt of prior allogeneic transplant did not independently impact response or leukemia-free survival (LFS). Concurrent IDH mutations were associated with lower CR/CRi (P = .01), while ASXL1 or TET2 mutations showed a non-significant association toward higher CR/CRi (P = .07, for both). However, none of the concurrent mutations were an independent predictor for response when adjusted to AML setting. In conclusion, VEN-HMA is associated with encouraging efficacy in FLT3m AML among both newly diagnosed unfit and r/r patients.
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http://dx.doi.org/10.1002/ajh.25929DOI Listing
July 2020

Iron Overload Is Associated with Delayed Engraftment and Increased Nonrelapse Mortality in Recipients of Umbilical Cord Blood Hematopoietic Cell Transplantation.

Biol Blood Marrow Transplant 2020 09 11;26(9):1697-1703. Epub 2020 Jun 11.

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California.

The negative impact of iron overload (IO) on outcomes of allogeneic hematopoietic cell transplantation (HCT) is well recognized, but its impact on umbilical cord blood (UCB) transplant outcome is unknown. We retrospectively analyzed outcomes of 150 patients who received UCB-HCT at our institution, stratified by pre-HCT serum ferritin (SF) level of 2000 ng/mL. Two-year overall survival rate among patients with SF >2000 and ≤2000 ng/mL was 26.1% (95% CI, 10.6% to 44.7%) and 52.1% (95% CI, 40.1% to 62.8%), respectively; hazard ratio (HR) = 2.26 (95% CI, 1.28 to 4.00, P = .005). Two-year nonrelapse mortality rate was higher among patients with SF >2000 ng/mL (56.5%; 95% CI, 33.3% to 74.4%) compared to SF ≤2000 ng/mL (30.1%; 95% CI, 20.0% to 40.9%); HR = 2.18 (95% CI, 1.10 to 4.31, P = .025). Neutrophil engraftment at 42 days was 78.3% (95% CI, 53.5% to 90.8%) in patients with SF >2000 ng/mL versus 91.8% (95% CI, 82.1% to 96.4%) in patients with SF ≤2000 ng/mL; HR = 0.58 (95% CI, 0.35 to 0.96, P = .034). A significant difference in platelet engraftment at 3 months was also observed: 52.2% (95% CI, 29.4% to 70.8%) for SF >2000 ng/mL versus 80.8% (95% CI, 69.5% to 88.3%) for SF ≤2000 ng/mL; HR = 0.48 (95% CI, 0.23 to 0.98, P = .044). In conclusion, IO defined by SF of 2000 ng/mL is a strong adverse prognostic factor for UCB-HCT and should be considered when UCB is chosen as the graft source for patients without a fully matched donor.
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http://dx.doi.org/10.1016/j.bbmt.2020.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486229PMC
September 2020

Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplant with Fludarabine and Melphalan Conditioning and Tacrolimus/Sirolimus as Graft-versus-Host Disease Prophylaxis in Patients with Acute Lymphoblastic Leukemia.

Biol Blood Marrow Transplant 2020 08 19;26(8):1425-1432. Epub 2020 May 19.

Department of Hematology and HCT, City of Hope, Duarte, California; Department of Computational Quantitative Medicine/BRI, City of Hope, Duarte, California. Electronic address:

Acute lymphoblastic leukemia (ALL) is associated with poor survival in older adults, and allogeneic hematopoietic cell transplant (HCT) with reduced-intensity conditioning (RIC) has been an increasingly used strategy in this population. At City of Hope we conducted a retrospective analysis of 72 patients who underwent allogeneic HCT with fludarabine and melphalan (FluMel) as the conditioning regimen between 2005 and 2018, from either a matched sibling or fully matched unrelated donor while in complete remission. Tacrolimus and sirolimus (T/S) were used as graft-versus-host disease (GVHD) prophylaxis. Overall survival and progression-free survival at 4 years post-HCT were 58% and 44%, respectively. The cumulative incidences of relapse/progression and nonrelapse mortality at 4 years were 34% and 22%, respectively. Patients with Philadelphia chromosome-positive (Ph+) ALL had a significantly lower cumulative incidence of relapse/progression (20% versus 48% for patients with Ph-negative status, P = .007). In conclusion, RIC HCT with FluMel conditioning and T/S GVHD prophylaxis was associated with favorable outcomes in patients with Ph+ ALL and should be considered as a viable consolidative therapy for adult patients with ALL.
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http://dx.doi.org/10.1016/j.bbmt.2020.04.015DOI Listing
August 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

Securing the graft during pandemic: are we ready for cryopreservation for all?

Biol Blood Marrow Transplant 2020 07 17;26(7):e145-e146. Epub 2020 Apr 17.

Department of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.

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http://dx.doi.org/10.1016/j.bbmt.2020.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162777PMC
July 2020

Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients: A Phase 2, Randomized Clinical Trial.

Ann Intern Med 2020 03 11;172(5):306-316. Epub 2020 Feb 11.

City of Hope Comprehensive Cancer Center and the Beckman Research Institute of City of Hope, Duarte, California (C.L., J.L., C.R.L., Q.Z., J.M., T.K., A.D., N.H., S.F., D.J.D.).

Background: Triplex vaccine was developed to enhance cytomegalovirus (CMV)-specific T cells and prevent CMV reactivation early after hematopoietic stem cell transplant (HCT).

Objective: To determine the safety and efficacy of Triplex.

Design: First-in-patient, phase 2 trial. (ClinicalTrials.gov: NCT02506933).

Setting: 3 U.S. HCT centers.

Participants: 102 CMV-seropositive HCT recipients at high risk for CMV reactivation.

Intervention: Intramuscular injections of Triplex or placebo were given on days 28 and 56 after HCT. Triplex is a recombinant attenuated poxvirus (modified vaccinia Ankara) expressing immunodominant CMV antigens.

Measurements: The primary outcomes were CMV events (CMV DNA level ≥1250 IU/mL, CMV viremia requiring antiviral treatment, or end-organ disease), nonrelapse mortality, and severe (grade 3 or 4) graft-versus-host disease (GVHD), all evaluated through 100 days after HCT, and grade 3 or 4 adverse events (AEs) within 2 weeks after vaccination that were probably or definitely attributable to injection.

Results: A total of 102 patients (51 per group) received the first vaccination, and 91 (89.2%) received both vaccinations (46 Triplex and 45 placebo). Reactivation of CMV occurred in 5 Triplex (9.8%) and 10 placebo (19.6%) recipients (hazard ratio, 0.46 [95% CI, 0.16 to 1.4]; P = 0.075). No Triplex recipient died of nonrelapse causes during the first 100 days or had serious AEs, and no grade 3 or 4 AEs related to vaccination were observed within 2 weeks after vaccination. Incidence of severe acute GVHD after injection was similar between groups (hazard ratio, 1.1 [CI, 0.53 to 2.4]; P = 0.23). Levels of long-lasting, pp65-specific T cells with effector memory phenotype were significantly higher in Triplex than placebo recipients.

Limitation: The lower-than-expected incidence of CMV events in the placebo group reduced the power of the trial.

Conclusion: No vaccine-associated safety concerns were identified. Triplex elicited and amplified CMV-specific immune responses, and fewer Triplex-vaccinated patients had CMV viremia.

Primary Funding Source: National Cancer Institute and Helocyte.
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http://dx.doi.org/10.7326/M19-2511DOI Listing
March 2020

Outcomes of Allogeneic Hematopoietic Cell Transplantation after Salvage Therapy with Blinatumomab in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia.

Biol Blood Marrow Transplant 2020 06 5;26(6):1084-1090. Epub 2020 Feb 5.

Department of Hematology and HCT, City of Hope, Duarte, California.

Historically, outcomes of adult patients with relapsed acute lymphoblastic leukemia (ALL) who fail to enter remission with conventional chemotherapy are very poor. Blinatumomab, a bispecific CD3/CD19 antibody, has shown remarkable activity in relapsed/refractory (r/r) ALL. Although allogeneic hematopoietic cell transplant (HCT) is the recommended consolidation therapy for patients with r/r ALL who respond to salvage therapy, HCT and toxicity outcomes for those who received blinatumomab salvage and HCT remain largely unknown. We treated 89 patients with r/r ALL with blinatumomab, of whom 43 patients (48%) achieved remission. Here we describe our single-center experience in the subset of patients who responded to blinatumomab salvage therapy for eradication of either gross (n = 24) or minimal residual disease (n = 11) before HCT. Overall survival at 1 and 2 years after allogeneic HCT was 77% and 52%, respectively. Leukemia-free survival at 1 and 2 years were 65% and 40%, respectively. Additionally, with blinatumomab administration pre-HCT, no unusual toxicities such as delayed neutrophil/platelet engraftment or graft failure were observed. Acute grades II to IV graft-versus-host disease (GVHD) at day +100 post-HCT was at 43% and 2-year chronic GVHD was 36%, both comparable with historic control subjects. Finally, results of our subset analysis based on pre-HCT minimal residual disease (MRD) status indicated no significant difference in survival outcomes among patients undergoing transplant in MRD-negative status and the entire cohort. In conclusion, based on results of this study, blinatumomab may be considered as a safe and effective agent for r/r ALL patients before HCT.
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http://dx.doi.org/10.1016/j.bbmt.2020.01.029DOI Listing
June 2020

Cost analysis of ganciclovir and foscarnet in recipients of allogeneic hematopoietic cell transplant with cytomegalovirus viremia.

Transpl Infect Dis 2020 Apr 30;22(2):e13233. Epub 2019 Dec 30.

Department of Medicine, Division of Infectious Disease, City of Hope, Duarte, California.

Background: Ganciclovir (GCV) and foscarnet (FOS) are the most commonly used antivirals for preemptive treatment of cytomegalovirus (CMV) viremia in recipients of allogeneic hematopoietic cell transplantation (alloHCT). The current literature indicates similar efficacy between these agents. Thus, the primary consideration for choice of initial anti-CMV treatment is the safety profile, time period after alloHCT, and concern of myelosuppression or renal dysfunction.

Methods: Herein, we retrospectively reviewed medical records of 124 alloHCT recipients who received GCV or FOS between April 27, 2014, and December 31, 2015, during the first year post-transplant. Healthcare resource use included drug, hospitalization, home health, dialysis, and growth factor costs.

Results: Total duration of therapy was longer in the GCV group (37 days vs 28 days, P = .21) but hospitalization days were similar (9 days) in both groups. The total treatment cost was significantly lower in the GCV group ($38 100 vs $59 400, P < .05).

Conclusion: Preemptive anti-CMV therapy is associated with major healthcare resource costs, which were greater in patients who required FOS than those who were treated with GCV.
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http://dx.doi.org/10.1111/tid.13233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162712PMC
April 2020

Invasive fungal infections in acute myeloid leukemia treated with venetoclax and hypomethylating agents.

Blood Adv 2019 12;3(23):4043-4049

Gehr Family Center for Leukemia Research, Department of Hematology and Hematopoietic Cell Transplantation.

The combination of venetoclax with hypomethylating agents (VEN-HMAs) showed promising activity in newly diagnosed and relapsed/refractory (r/r) acute myeloid leukemia (AML). Treatment with VEN-HMAs results in prolonged cytopenia, thereby exposing patients to invasive fungal infections (IFIs). Here, we retrospectively studied a cohort of 119 AML patients treated with VEN-HMAs and analyzed the occurrence of IFIs, as well as our practice of antifungal prophylaxis, with the aim to identify the nature and risk factors for IFIs and their association with the type of antifungal prophylaxis used. The intended antifungal prophylaxis was micafungin in 38% of patients, azoles in 41% of patients, and none in 21% of patients. Older age was associated with no antifungal prophylaxis or micafungin use and lesser use of azoles (P = .043). We recorded 15 (12.6%) patients who developed probable or proven IFIs, with a median onset of 72 days (range, 35-281) after starting therapy. IFIs were more common among nonresponders compared with responders to VEN-HMA therapy (22% vs 6%, P = .0132) and in r/r compared with newly diagnosed AML (19% vs 5%, P = .0498); however, the antifungal prophylaxis used, patient age, hypomethylating agent schedule, history of prior allogeneic transplant, and initial neutropenia duration did not influence the development of IFIs during therapy. We conclude that the overall risk of IFIs during VEN-HMA therapy is low. The risk of IFIs is higher in nonresponders and in those who were treated in the r/r setting; these patients need reevaluation of their antifungal prophylaxis to minimize the risk of IFIs during therapy.
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http://dx.doi.org/10.1182/bloodadvances.2019000930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963254PMC
December 2019

RBC and platelet transfusion support in the first 30 and 100 days after haploidentical hematopoietic stem cell transplantation.

Transfusion 2019 11 10;59(11):3371-3385. Epub 2019 Oct 10.

Division of Transfusion Medicine, Department of Pathology, City of Hope National Medical Center, Duarte, California.

Background: The volume of haploidentical hematopoietic stem cell transplant (haplo-HSCT) has increased dramatically in recent years. However, the associated higher risk of delayed engraftment may increase patient transfusion requirements.

Study Design And Methods: The post-HSCT RBC and platelet transfusions of 195 haplo-HSCT recipients were evaluated. Patient and transplant-related factors potentially impacting the number of products transfused and time to transfusion independence were assessed.

Results: Nearly all (98.4%) patients were transfused in the first 30 days, and 59.2% were transfused between days 31 and 100. Among the transfused patients, medians of 5 units (interquartile range [IQR] = 3-8) of RBCs and 11 units (6-20) platelets were given in the first 30 days, and medians of 3 units (IQR = 1-7) of RBCs and 6 units (2-18) of platelets were transfused between days 31 and 100. Median times for achieving RBC and platelet transfusion independence were 34 (95% CI: 28-40) and 25 (95% CI: 23-27) days, respectively. Multivariable analyses showed that RBC transfusions in the 10 days before HSCT were associated with significantly increased and sustained RBC and platelet transfusion requirements. Major ABO incompatibility led to increased RBC transfusions. Advanced disease was associated with increased transfusions during the first 30 days, whereas GVHD increased platelet transfusions between days 31 and 100. Effects of age, sex, CD34+ cell dose, stem cell source, and conditioning regimen were limited or insignificant.

Conclusions: This study for the first time provided quantitative transfusion data on a large cohort of haplo-HSCT recipients and identified factors predictive of increased transfusions.
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http://dx.doi.org/10.1111/trf.15531DOI Listing
November 2019

Myeloablative vs reduced intensity T-cell-replete haploidentical transplantation for hematologic malignancy.

Blood Adv 2019 10;3(19):2836-2844

Center for International Blood and Marrow Transplant Research, and.

In the absence of prospective studies that examine the effect of conditioning regimen intensity after T-cell-replete haploidentical transplant for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS), a retrospective cohort analysis was performed. Of the 1325 eligible patients (AML, n = 818; ALL, n = 286; and MDS, n = 221), 526 patients received a myeloablative regimen and 799 received a reduced-intensity regimen. Graft-versus-host disease prophylaxis was uniform with posttransplant cyclophosphamide, a calcineurin inhibitor, and mycophenolate mofetil. The primary end point was disease-free survival. Cox regression models were built to study the effect of conditioning regimen intensity on transplant outcomes. For patients aged 18 to 54 years, disease-free survival was lower (hazard ratio [HR], 1.34; 42% vs 51%; = .007) and relapse was higher (HR, 1.51; 44% vs 33%; = .001) with a reduced-intensity regimen compared with a myeloablative regimen. Nonrelapse mortality did not differ according to regimen intensity. For patients aged 55 to 70 years, disease-free survival (HR, 0.97; 37% vs 43%; = .83) and relapse (HR, 1.32; 42% vs 31%; = .11) did not differ according to regimen intensity. Nonrelapse mortality was lower with reduced-intensity regimens (HR, 0.64; 20% vs 31%; = .02). Myeloablative regimens are preferred for AML, ALL, and MDS; reduced-intensity regimens should be reserved for those unable to tolerate myeloablation.
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http://dx.doi.org/10.1182/bloodadvances.2019000627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784523PMC
October 2019

Protective effect of HLA-DPB1 mismatch remains valid in reduced-intensity conditioning unrelated donor hematopoietic cell transplantation.

Bone Marrow Transplant 2020 02 24;55(2):409-418. Epub 2019 Sep 24.

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.

A mismatch at HLA-DPB1 locus is associated with higher acute GVHD and lower relapse rate after myeloablative (MAC) allogeneic hematopoietic cell transplantation (alloHCT). Also, in MAC setting, mismatch permissiveness and expression level impact alloHCT outcomes. However, in reduced intensity conditioning (RIC), DP mismatch effect on transplant outcomes is unknown. We retrospectively evaluated DP mismatch influence (number, permissiveness, and expression) on HCT outcomes in 310 patients with high-resolution typing (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1), who underwent RIC HCT. By multivariable analysis, 11/12 had better overall survival (OS) and relapse vs. 12/12 (HR = 1.61 and 2.02; p = 0.04 and 0.01, respectively) and better OS vs. 10/12 (HR = 1.68; p = 0.02). Within the 11/12, nonpermissive (NoPR) mismatch was associated with higher risk of grade II-IV acute GVHD (HR = 1.97; p = 0.005) and nonrelapse mortality (HR = 2.13; p = 0.02) vs. permissive (PR). Grouping 11/12 based on the DP expression conferred higher mortality (HR = 3.78; p = 0.003) when low expressers received a graft from high expressers (AG) vs. low expressers (AA). Better OS was achieved in PR 11/12, when expression was low in patient and donor (AA) vs. all other combinations. Therefore, in RIC HCT, a single-DP mismatch has a protective role, especially in permissive setting, when donor and recipient are low expressers.
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http://dx.doi.org/10.1038/s41409-019-0694-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002238PMC
February 2020

Clinical applications of donor lymphocyte infusion from an HLA-haploidentical donor: consensus recommendations from the Acute Leukemia Working Party of the EBMT.

Haematologica 2020 01 19;105(1):47-58. Epub 2019 Sep 19.

Dept. of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie Institute - Oncology Center, Gliwice Branch, Gliwice, Poland.

Donor lymphocyte infusion has been used in the management of relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. It can eradicate minimal residual disease or be used to rescue a hematologic relapse, being able to induce durable remissions in a subset of patients. With the increased use of haploidentical hematopoietic cell transplantation, there is renewed interest in the use of donor lymphocytes to either treat or prevent disease relapse post transplant. Published retrospective and small prospective studies have shown encouraging results with therapeutic donor lymphocyte infusion in different haploidentical transplantation platforms. In this consensus paper, finalized on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize the available evidence on the use of donor lymphocyte infusion from haploidentical donor, and provide recommendations on its therapeutic, pre-emptive and prophylactic use in clinical practice.
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http://dx.doi.org/10.3324/haematol.2019.219790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939532PMC
January 2020

Long-Term Outcomes of Patients with Acute Myelogenous Leukemia Treated with Myeloablative Fractionated Total Body Irradiation TBI-Based Conditioning with a Tacrolimus- and Sirolimus-Based Graft-versus-Host Disease Prophylaxis Regimen: 6-Year Follow-Up from a Single Center.

Biol Blood Marrow Transplant 2020 02 16;26(2):292-299. Epub 2019 Sep 16.

Department of Hematology and HCT, City of Hope, Duarte, California.

Cyclophosphamide (Cy)/etoposide combined with fractionated total body irradiation (FTBI) or i.v. busulfan (Bu) has been the main conditioning regimens for allogeneic hematopoietic cell transplantation (alloHCT) for young patients with acute myelogenous leukemia (AML) eligible for a myeloablative conditioning (MAC) regimen. Recent data has suggested that i.v. Bu could be the preferred myeloablative regimen in patients with myeloid malignancies. However, Bu-based regimens are associated with higher rates of sinusoidal obstruction syndrome. Here we report long-term survival outcomes of patients with AML receiving FTBI combined with Cy or etoposide before undergoing alloHCT at City of Hope (COH). We obtained a retrospective review of a prospectively maintained institutional registry of clinical outcomes in 167 patients (median age, 41 years; range, 18 to 57 years) with AML in first or second complete remission who underwent alloHCT at COH between 2005 and 2015. Eligible patients received a MAC regimen with FTBI (1320 cGy) and Cy (120 mg/kg) for unrelated donor transplantation or etoposide (60 mg/kg) for related donor transplantation. Graft-versus-host disease (GVHD) prophylaxis was provided with tacrolimus and sirolimus. In this retrospective study, 6-year overall survival was 60% and nonrelapse mortality was 15%. The GRFS rate was 45% at 1 year and 39% at 2 years. We also describe late metabolic effects and report the cumulative incidence of secondary malignancies (9.5%). Overall, in this young adult patient population, our results compare favorably to chemotherapy-based (i.v. Bu) conditioning regimens without significant long-term toxicity arising from TBI-based regimens.
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http://dx.doi.org/10.1016/j.bbmt.2019.09.017DOI Listing
February 2020

Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation From Unrelated Donor Using Tacrolimus/Sirolimus-based GvHD Prophylaxis: Impact of HLA Mismatch.

Transplantation 2020 05;104(5):1070-1080

Department of Hematology and Hematopoietic Stem Cell Transplantation, City of Hope, Duarte, CA.

Background: While tacrolimus and sirolimus (T/S)-based graft-versus-host disease (GvHD) prophylaxis has been effective in preventing acute GvHD post hematopoietic cell transplantation (HCT), its efficacy and long-term outcome in matched (MUD) and mismatched unrelated donor (mMUD) setting is not well defined.

Methods: Herein, we evaluated a consecutive case-series of 482 patients who underwent unrelated donor HCT (2005-2013) with T/S-based GvHD prophylaxis.

Results: With a median follow-up of 6.2 years (range = 2.4-11.3), the 5-year overall survival (OS) and relapse/progression-free survival were 47.5% (95% confidence interval [CI]: 43.0-52.0) and 43.6% (95% CI: 39.1-48.1), respectively; and the 5-year cumulative incidence of nonrelapse mortality (NRM) and relapse were 24.9%, and 31.5%, respectively. In this cohort, mMUD was associated with worse OS (39.0% versus 50.7% at 5 y; P = 0.034), primarily due to greater risk of NRM (33.5% versus 21.7%; P = 0.038). While rates of relapse, acute (II-IV or III-IV) or chronic GvHD (limited or extensive) were not different, death caused by chronic GvHD (20.8% versus 12.8%; P = 0.022) and infection (33.0% versus 18.1%; P < 0.01) were significantly greater in mMUD. In multivariable analysis, high-risk disease (hazard ratio [HR] = 2.21, 95% CI: 1.16-4.23; P < 0.01) and mMUD (HR = 1.55, 95% CI: 1.15-2.08; P = 0.004) were independent predictive factors for OS.

Conclusions: T/S-based GvHD prophylaxis is an effective and acceptable GvHD prophylactic regimen. However, survival after mMUD remained poor, possibly related to the severity of chronic GvHD.
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http://dx.doi.org/10.1097/TP.0000000000002932DOI Listing
May 2020

Allogeneic Hematopoietic Cell Transplantation Outcomes in Patients Carrying Isocitrate Dehydrogenase Mutations.

Clin Lymphoma Myeloma Leuk 2019 07 26;19(7):e400-e405. Epub 2019 Apr 26.

Department of Hematology and HCT, City of Hope National Medical Center, Duarte, CA.

Background: Mutations in isocitrate dehydrogenase (IDH)1/2 genes result in nicotinamide adenine dinucleotide phosphate-dependent reduction of α-ketoglutarate and formation of 2-hydroxyglutarate, which blocks normal cellular differentiation and promotes leukemogenesis. Nearly 20% of acute myeloid leukemia (AML) patients carry IDH1/2 mutations. Although multiple investigators have described the prognostic implications of IDH mutations in AML patients receiving chemotherapy, the effect of these mutations on outcomes after allogeneic (allo) hematopoietic cell transplantation (HCT) is unknown.

Patients And Methods: We report on the clinical outcome of a cohort of AML patients, who were tested for IDH mutations and underwent alloHCT at City of Hope (2015-2017). Of a total of 317 screened patients, 99 (31%) underwent alloHCT, of whom 23 carried and 76 did not carry IDH mutations (control).

Results: No statistical significance was detected in patient's overall survival (P = .84). With a median follow-up of 7.8 months, 1-year relapse rate of 29% and 13% was seen in the IDH-mutated and control group, respectively (P = .033). IDH1/2 mutation status remained significantly associated with relapse (hazard ratio, 2.8; P = .046) after inclusion of pre-HCT disease status in a multivariable model.

Conclusion: Our results, despite low patient numbers, indicate that IDH mutations are associated with higher relapse rate after alloHCT. Further prospective studies on post transplantation IDH inhibition is required to improve outcomes in AML patients who carry IDH mutations.
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http://dx.doi.org/10.1016/j.clml.2019.04.007DOI Listing
July 2019

The European Society for Blood and Marrow Transplantation (EBMT) consensus recommendations for donor selection in haploidentical hematopoietic cell transplantation.

Bone Marrow Transplant 2020 01 4;55(1):12-24. Epub 2019 Mar 4.

Acute Leukemia Working Party of the EBMT, Hopital Saint-Antoine, Paris, France.

The number of HLA-haploidentical hematopoietic cell transplants continues to increase worldwide due to recent improvements in outcomes, allowing more patients with hematological malignancies and non-malignant disorders to benefit from this procedure and have a chance to cure their disease. Despite these encouraging results, questions remain as multiple donors are usually available for transplantation, and choosing the best HLA-haploidentical donor for transplantation remains a challenge. Several approaches to haploidentical transplantation have been developed over time and, based on the graft received, can be grouped as follows: T-cell depleted haploidentical transplants, either complete or partial, or with T-cell replete grafts, performed with post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, or G-CSF-primed bone marrow graft and enhanced GVHD prophylaxis. Carefully selecting the donor can help optimize transplant outcomes for recipients of haploidentical donor transplants. Variables usually considered in the donor selection include presence of donor-specific antibodies in the recipient, donor age, donor/recipient gender and ABO combinations, and immunogenic variables, such as natural killer cell alloreactivity or KIR haplotype. Here we provide a comprehensive review of available evidence for selecting haploidentical donors for transplantation, and summarize the recommendations from the European Society for Blood and Marrow Transplantation (EBMT) on donor selection for different transplant platforms.
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http://dx.doi.org/10.1038/s41409-019-0499-zDOI Listing
January 2020

PTCy-based haploidentical vs matched related or unrelated donor reduced-intensity conditioning transplant for DLBCL.

Blood Adv 2019 02;3(3):360-369

Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.

This study retrospectively compared long-term outcomes of nonmyeloablative/reduced intensity conditioning (NMC/RIC) allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical family donor (haplo-HCT) using posttransplant cyclophosphamide (PTCy) with those of matched sibling donor (MSD) and matched unrelated donor (MUD) with or without T-cell depletion (TCD+/TCD-) in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adult patients with DLBCL who had undergone their first NMC/RIC allo-HCT between 2008 and 2015 were included. Recipients of haplo-HCT were limited to those receiving graft-versus-host disease (GVHD) prophylaxis with PTCy. GVHD prophylaxis in MSD was limited to calcineurin inhibitor (CNI)-based approaches without in vivo TCD, while MUD recipients received CNI-based prophylaxis with or without TCD. Outcome analyses for overall survival (OS) and progression-free survival (PFS), nonrelapse mortality (NRM), and disease relapse/progression were calculated. A total of 1438 patients (haplo, 132; MSD, 525; MUD TCD+, 403; and MUD TCD-, 378) were included. Patients with haplo donors were significantly older, had a better performance status and had more frequently received total body irradiation-based conditioning regimens and bone marrow grafts than MSD and MUD TCD+ or TCD-. 3-year OS, PFS, NRM and relapse/progression incidence after haplo-HCT was 46%, 38%, 22%, and 41%, respectively, and not significantly different from outcomes of matched donor transplants on multivariate analyses. Haplo-HCT was associated with a lower cumulative incidence of chronic GVHD compared with MSD, MUD TCD+/TCD-. NMC/RIC haplo-HCT with PTCy seems to be a valuable alternative for patients with DLBCL considered for allo-HCT but lacking a matched donor.
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http://dx.doi.org/10.1182/bloodadvances.2018027748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373757PMC
February 2019

Post-Allogeneic Hematopoietic Stem Cell Transplantation Eculizumab as Prophylaxis Against Hemolysis and Thrombosis for Patients with Hematologic Disorders Associated with Paroxysmal Nocturnal Hemoglobinuria Clones.

Biol Blood Marrow Transplant 2019 05 29;25(5):e183-e185. Epub 2019 Jan 29.

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California; Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope, Duarte, California.

Paroxysmal nocturnal hemoglobinuria (PNH) is frequently seen in the context of other aplastic anemia and myelodysplastic syndromes and is associated with hemolysis and increased thromboembolic events. Allogeneic hematopoietic stem cell transplantation (alloHCT) is the sole curative treatment but is associated with significant morbidity. The terminal complement inhibitor eculizumab reduces hemolysis and thromboembolic events and is the sole Food and Drug Administration-approved therapy for PNH. Prophylactic administration of this agent in the early post-transplantation setting to prevent hemolysis and thrombosis has not been described in the literature. We describe our institutional experience of 8 patients with PNH who underwent alloHCT and who received at least 1 dose of eculizumab within 30 days of alloHCT for prevention of thrombosis and hemolysis. One patient with underlying aplastic anemia who received bone marrow stem cells failed to engraft. Another patient experienced steroid-refractory grade IV acute graft-versus-host disease and died of a fungal infection. The other patients engrafted well; no hemolysis, thrombotic events, or infections associated with encapsulated bacteria occurred in any of the 8 patients.
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http://dx.doi.org/10.1016/j.bbmt.2019.01.025DOI Listing
May 2019
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