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Endothelial Activation and Stress Index in adults undergoing allogeneic hematopoietic cell transplantation with post-transplant cyclophosphamide-based prophylaxis
Escribano-Serrat, S., Rodríguez-Lobato, L. G., Charry, P., Martínez-Cibrian, N., Suárez-Lledó, M., Rivero, A., Moreno-Castaño, A. B., Solano, M. T., Arcarons, J., Nomdedeu, M., et al
Cytotherapy. 2023
Abstract
BACKGROUND AIMS Post-transplant cyclophosphamide (PTCY)-based prophylaxis is becoming widespread for allogeneic hematopoietic cell transplantation (allo-HCT) performed independently of the selected donor source. In parallel, use of the Endothelial Activation and Stress Index (EASIX)-considered a surrogate parameter of endothelial activation-for predicting patient outcomes and clinical complications is gaining popularity in the allo-HCT setting. METHODS We first investigated whether the dynamics of EASIX after allo-HCT differ between patients receiving PTCY and patients receiving other prophylaxis. We then investigated whether the predictive capacity of EASIX persists in PTCY-based allo-HCT. A total of 328 patients transplanted between 2014 and 2020 were included, and 201 (61.2%) received PTCY. RESULTS EASIX trends differed significantly between the groups. Compared with patients receiving other prophylaxis, patients receiving PTCY had lower EASIX on day 0 and higher values between day 7 and day 100. In patients receiving PTCY, higher EASIX correlated significantly with higher non-relapse mortality (NRM) and lower overall survival (OS) when measured before and during the first 180 days after allo-HCT. In addition, higher EASIX scores measured at specific time points were predictors of veno-occlusive disease (VOD), transplant-associated thrombotic microangiopathy (TA-TMA) and grade 2-4 acute graft-versus-host disease (aGVHD) risk. CONCLUSIONS This study demonstrates how EASIX trends vary during the first 180 days after allo-HCT in patients receiving PTCY and those not receiving PTCY and validates the utility of this index for predicting NRM, OS and risk of VOD, TA-TMA and grade 2-4 aGVHD in patients receiving PTCY.
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Post-transplant Cyclophosphamide and Tacrolimus for GVHD Prevention Allo-HCT from HLA-Matched Donors Generates more Advantages than Limitations
Salas, M. Q., Pedraza, A., Charry, P., Suárez-Lledó, M., Rodríguez-Lobato, L. G., Brusosa, M., Solano, M. T., Serrahima, A., Nomdedeu, M., Cid, J., et al
Transplantation and cellular therapy. 2023
Abstract
This study compares the efficacy of PTCY/Tac vs. other prophylaxis in 272 adults undergoing peripheral blood (PB) allo-HCT from HLA-matched donors. 95 (34.9%) adults received PTCY/Tac. Time to neutrophil and platelet engraftment was longer in the PTCY/Tac group (20 vs. 16 days and 19 vs. 12 days). The day +30 cumulative incidence of bacterial bloodstream infection was higher in the PTCY/Tac group (43.2% vs. 13.0%, P<0.001). The cumulative incidences of grade II-IV and III-IV aGVHD at day +180 and of moderate/severe cGVHD at 2 years were 14.7%, 4.2%, and 2.4% for patients receiving PTCY/Tac, and 41.8% (HR 0.29, P<0.001), 15.8%, (HR 0.24, P=0.007) and 47.0% (HR 0.05, P<0.001) for those who did not. Immunosuppression duration was shorter in patients receiving PTCY/Tac (6.2 vs. 9.0 months, P<0.001). PTCY/Tac patients had higher OS (2-years: 74.3 vs. 60.9%, HR 0.54, P=0.012), lower NRM (2-years: 8.6% vs. 15.8%; HR 0.54, P=0.11), comparable CIR (2-years: 26.0% vs. 24.4%, HR 1.03, P=0.89), and higher GRFS (2-years: 59.1% vs. 16.7%; HR 0.32, P<0.001). Using PTCY/Tac in HLA-matched PB allo-HCT improved transplant outcomes at out institution, compared with that of previous prophylaxis, including higher probability of survival in spite of more delayed engraftment and higher bacterial infections.
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Effect of CD34+ cell dose on the outcomes of allogeneic stem cell transplantation with post-transplant cyclophosphamide
Pedraza, A., Salas, M. Q., Rodríguez-Lobato, L. G., Charry, P., Suárez-Lledo, M., Martínez, N., Doménech, A., Solano, M. T., Arcarons, J., de Llobet, N., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND The impact of infused CD34+ cell dose on the outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) using standard graft-versus-host disease (GVHD) prophylaxis remains controversial. Information on this subject is scarce for alloHSCT using high-dose post-transplant cyclophosphamide (PTCy). OBJECTIVES We aim to assess the effect of CD34+ cell dose in peripheral blood stem cells (PBSC) grafts on the outcome of alloHSCT using PTCy-based GVHD prophylaxis. STUDY DESIGN We conducted a single center retrospective analysis on 221 consecutive adult patients who received PTCy alloHSCT from HLA-matched sibling donors (MSD) (N=22), HLA-matched (MUD) (N=83), mismatched unrelated donors (MMUD) (N=73), and haploidentical donors (N=43). Based on the binary partitioning method, 5 × 10(6)/kg was used as the optimal cut-off of CD34+ cell dose. According to our institutional protocol, the maximum CD34+ cell dose was capped at 8 × 10(6)/kg. The study cohort was separate in two groups: CD34+ cells high-dose (> 5 to 8 × 10(6)/kg) and low-dose (≤ 5 × 10(6)/kg). RESULTS Patients receiving high-dose CD34+ containing grafts had a significantly shorter median time to neutrophil (19 vs. 21 days, P=0.002) and platelet engraftment (16 vs. 22 days, P=0.04) compared to those who received low-dose CD34+. No differences between high-dose and low-dose groups were observed in the cumulative incidence of day +100 acute GVHD (grade II-IV: 25% vs. 23%, P=0.7; and grade III-IV: 5% vs. 4%, respectively, P=0.4), or 2-year chronic GVHD (moderate/severe GVHD 9% vs. 6%, P=0.5). No impact of CD34+ cell dose on survival outcomes when using MSD, MUD or MMUD was observed. Recipients of haploidentical alloHSCT using low-dose CD34+ cell had significant worse overall survival (HR 6.01, P=0.004) and relapse free survival (HR 4.57, P=0.004). CONCLUSIONS In patients receiving PBSC PTCy alloHSCT, infused CD34+ cell doses > 5 to 8 × 10(6)/kg was associated with faster neutrophil and platelet engraftment, independently of the type of donor. Our study suggest an impact of CD34+ cell dose on survival outcomes only with haploidentical donors, for whom the administration of a CD34+ cell dose ≤ 5 × 10(6)/kg significantly decreased survival outcomes.
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Posttransplant cyclophosphamide-based anti-graft-vs-host disease prophylaxis in patients with acute lymphoblastic leukemia treated in complete remission with allogeneic hematopoietic cell transplantation from human leukocyte antigen-mismatched unrelated donors versus haploidentical donors: A study on behalf of the ALWP of the EBMT
Nagler, A., Labopin, M., Arat, M., Reményi, P., Koc, Y., Blaise, D., Angelucci, E., Vydra, J., Kulagin, A., Socié, G., et al
Cancer. 2022
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Editor's Choice
Abstract
BACKGROUND Both mismatched unrelated donor (MMUD) and haploidentical (haplo) transplantation are valid options in patients with high-risk acute lymphoblastic leukemia (ALL) lacking a matched donor. METHODS The study compared the outcomes of adult patients with ALL in complete remission (CR) who underwent 9/10 MMUD versus haplo transplantation with posttransplant cyclophosphamide (PTCy) as graft-vs-host disease (GVHD) prophylaxis in 2010-2020. RESULTS The study included 781 patients (MMUD, 103; haplo, 678). The median age was 40 (19-73) and 38 (18-75) years, respectively (p = .51). The most frequent immunosuppression agents added to PTCy were mycophenolate mofetil (MMF)/cyclosporine A and MMF/tacrolimus. In vivo T-cell depletion (anti-thymocyte globulin) was administered to 21% and 8% of the transplants, respectively (p < .0001). Neutrophil (absolute neutrophil count >0.5 × 10(9) /L) recovery was achieved in 97.1% versus 96.7% versus (p = 1) in MMUD and haplo, respectively. Nonrelapse mortality and relapse incidence were not significantly different between MMUD and haplo, hazard ratio (HR) = 1.45 (95% confidence interval [CI], 0.81-2.62; p = .21) and HR = 0.81 (95% CI, 0.52-1.28, p = .38), respectively. HRs for leukemia-free survival, overall survival, and GVHD-free, relapse-free survival were respectively, HR = 1.05 (95% CI, 0.73-1.50, p = .8), HR = 1.17 (95% CI, 0.77-1.76, p = .46), and HR = 1.07 (95% CI, 0.78-1.46, p = .7) for haplo compared to MMUD. Acute (a)GVHD grade 2-4 was significantly higher with haplo, HR = 1.73 (95% CI, 1.08-2.76, p = .023), whereas aGVHD grade 3-4 and chronic GVHD did not differ significantly between the two transplant groups. CONCLUSION Outcomes of MMUD and haplo transplants with PTCy-based GVHD prophylaxis for ALL patients in CR are similar, apart from a higher incidence of aGVHD with haplo transplants.
PICO Summary
Population
Adults with high-risk acute lymphoblastic leukemia (ALL) in complete remission, lacking a matched donor (n=781)
Intervention
9/10 mismatched unrelated donor transplantation (MMUD, n=103)
Comparison
Haploidentical transplantation (haplo, n=678)
Outcome
Neutrophil (absolute neutrophil count >0.5 × 10(9) /L) recovery was achieved in 97.1% versus 96.7% versus in MMUD and haplo, respectively. Nonrelapse mortality and relapse incidence were not significantly different between MMUD and haplo, hazard ratio (HR) = 1.45 (95% confidence interval [CI], 0.81-2.62) and HR = 0.81 (95% CI, 0.52-1.28), respectively. HRs for leukemia-free survival, overall survival, and GVHD-free, relapse-free survival were respectively, HR = 1.05 (95% CI, 0.73-1.50), HR = 1.17 (95% CI, 0.77-1.76), and HR = 1.07 (95% CI, 0.78-1.46) for haplo compared to MMUD. Acute (a)GVHD grade 2-4 was significantly higher with haplo, HR = 1.73 (95% CI, 1.08-2.76), whereas aGVHD grade 3-4 and chronic GVHD did not differ significantly between the two transplant groups.
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Bacterial Bloodstream Infections in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide
Salas, M. Q., Charry, P., Alcalde, P. P., Cibrian, N. M., Solano, M. T., Serrahima, A., Nomdedeu, M., Cid, J., Lozano, M., Chumbinta, M., et al
Transplantation and cellular therapy. 2022
Abstract
This study investigates the incidence and predictors for bacterial bloodstream infection (BSI) in 330 adults undergoing allo-HCT, and explores the effect of PTCY on the probability of presenting this complication. All patients received levofloxacin during the aplastic phase. Only the first episode of BSI was accounted as an event. Patients were classified into two groups: PTCY-based (n=200) vs. other prophylaxis (n=130). 124 patients were diagnosed with a first episode of BSI, most of them during the first 30 days (70.2%). Proportions of BSIs caused by Gram-positive bacteria were comparable to those caused by Gram-negative bacteria (48.3% vs. 45.9%). The cumulative incidence of BSI was higher in patients receiving PTCY than in those receiving other prophylaxis (Day +30 and +100: 35.0% and 37.0% vs. 13.1% and 18.5%, P<0.001). At day +30, the likelihood of BSI was 2.41 (P=0.012) times higher in the PTCY's than in the non-PTCY's group. The day 30 mortality rate in all patients with BSI was 8.0%, lower (P=0.002) in the PTCY's group (2.3%) than in the non-PTCY's one (21.6%). Finally, the overall survival of patients receiving PTCY and diagnosed with BSI was similar to that of patients without presenting this complication.
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PTCY and Tacrolimus for GVHD Prevention for Older Adults Undergoing HLA-Matched Sibling and Unrelated Donor AlloHCT
Salas, M. Q., Charry, P., Pedraza, A., Martínez-Cibrian, N., Solano, M. T., Domènech, A., Suárez-Lledó, M., Nomdedeu, M., Cid, J., Lozano, M., et al
Transplantation and cellular therapy. 2022
Abstract
INTRODUCTION The use of PTCY for graft-versus-host disease (GHVD) prevention is becoming prevalent in the transplant community when HLA-identical sibling (MSD) and 10/10 HLA-matched (MUD) and 9/10 mismatched (MMUD) unrelated donors are selected for alloHSCT. However, reported evidence on outcomes from elderly receiving PTCY-containing GVHD prophylaxis remains limited. OBJECTIVES This study aims to compare the outcomes of PTCY-TK prophylaxis and conventional GVHD prophylaxis in patients aged >50 years undergoing peripheral blood alloHSCT from a single institution. STUDY DESIGN A total of 161 consecutive patients aged >50 years undergoing alloHSCT between Jan-2014 and Feb-2021 were included. Data was collected retrospectively and updated in December 2021. Patients received grafts from HLA-identical sibling (MSD), and from 10/10 and 9/10 HLA matched and mismatched unrelated donors (UD). RESULTS Overall, median age was 60 years and 91 (54.8%) received PTCY-TK for GVHD prevention. Time to neutrophil and platelet engraftment was longer in the PTCY-TK group (20 vs. 16 days and 19 vs. 11 days, P< 0.001). The cumulative incidences of grade II-IV and III-IV aGVHD at day +100 and moderate/severe cGVHD at 2 years were 18.2%, 5.7% and 9.5% for patients receiving PTCY-TK, and 26.0%, 9.6% and 39.5% for those that did not. The multivariate analysis showed that PTCY-TK reduced the probability of grade II-IV aGVHD (HR 0.41, p=0.035), of cGVHD [any grade: HR 0.43 (p=0.014), and of moderate/severe cGVHD (HR 0.15 (p<0.001)]. At 2-years, the overall survival (65.4% vs. 65.6%, p=0.472), non-relapse mortality (17.4% vs. 13.7%, p=0.967), and cumulative incidence of relapse rates (24.2% vs. 27.5%, p=0.712) were comparable between both cohorts; GVHD-Free/Relapse-free survival (GRFS) was higher in the PTCY-TK group (2-years: 50.2% vs. 21.8%; HR 0.42, p=0.001). In patients aged ≥50 years, Conclusion: PTCY-TK was safe and a more effective drug combination than non-PTCY containing GVHD prophylaxis, even with the use of matched and mismatched UD, and resulted in comparable relapse rates and better GRFS.
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Should anti-thymocyte globulin be added in post-transplant cyclophosphamide based matched unrelated donor peripheral blood stem cell transplantation for acute myeloid leukemia? A study on behalf of the Acute Leukemia Working Party of the EBMT
Spyridonidis, A., Labopin, M., Brissot, E., Moiseev, I., Cornelissen, J., Choi, G., Ciceri, F., Vydra, J., Reményi, P., Rovira, M., et al
Bone marrow transplantation. 2022
Abstract
In this registry-based study which includes acute myeloid leukemia patients who underwent a matched unrelated donor allogeneic peripheral-blood stem cell transplantation in complete remission and received post-transplant cyclophosphamide (PTCY) as graft-versus-host disease (GvHD) prophylaxis, we compared 421 recipients without anti-thymocyte globulin (ATG) with 151 patients with ATG. The only significant differences between PTCY and PTCY + ATG cohorts were the median year of transplant and the follow-up period (2017 vs 2015 and 19.6 vs 31.1 months, respectively, p < 0.0001). Overall, 2-year survival was 69.9% vs 67.1% in PTCY and PTCY + ATG, respectively, with deaths related to relapse (39% vs 43.5%), infection (21.9% vs 23.9%) or GvHD (17.1% vs 17.4%) not differing between groups. On univariate comparison, a significantly lower rate of extensive chronic GvHD was found when ATG was added (9.9% vs 21%, p = 0.029), a finding which was not confirmed in the multivariate analysis. The Cox-model showed no difference between PTCY + ATG and PTCY alone with respect to acute and chronic GvHD of all grades, non-relapse mortality, relapse, leukemia-free survival, overall survival, and GvHD-free-relapse-free survival between study cohorts. Our results highlight that the addition of ATG in PTCY does not provide any extra benefit in terms of further GvHD reduction, better GRFS or better survival.
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Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the EBMT
Battipaglia, G., Galimard, J. E., Labopin, M., Raiola, A. M., Blaise, D., Ruggeri, A., Koc, Y., Gülbas, Z., Vitek, A., Sica, S., et al
Bone marrow transplantation. 2022
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Editor's Choice
Abstract
Whether to choose Haploidentical (Haplo) or one-antigen mismatched unrelated donor (1Ag-MMUD) hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) remains an unanswered question. We compared PTCy- Haplo-HCT to PTCy-1Ag-MMUD-HCT for acute myeloid leukemia (AML) in complete remission (three groups: 1Ag-MMUD using peripheral blood (1Ag-MMUD-PB; n = 155); Haplo using bone marrow (Haplo-BM; n = 647) or peripheral blood (Haplo-PB; n = 949)). Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.28, 95% CI 1.23-4.24, p < 0.01; HR 2.65, 95% CI 1.46-4.81, p < 0.01, respectively). Haplo groups experienced a lower leukemia-free survival (LFS) compared to 1Ag-MMUD-PB (Haplo-BM: HR 1.51, 95% CI 1.06-2.14, p = 0.02; Haplo-PB: 1.47, 95% CI 1.05-2.05, p = 0.02); overall survival (OS) was also lower in Haplo-HCT (Haplo-BM: HR 1.50, 95% CI 1.02-2.21, p = 0.04; Haplo-PB: HR 1.51, 95% CI 1.05-2.19, p = 0.03). No differences were observed for graft-versus-host/relapse-free survival (GRFS) and relapse incidence (RI). Haplo-BM was associated with a lower risk of grade III-IV acute graft-versus-host disease (GVHD) (HR 0.44, 95% CI 0.24-0.81; p < 0.01), while no statistical differences were observed between groups for grade II-IV aGVHD and for cGVHD. Use of PTCy in 1Ag-MMUD-HCT is a valid alternative to consider when using alternative donors. Larger analysis of 1Ag-MMUD versus Haplo-HCT are warranted.
PICO Summary
Population
Adults with acute myeloid leukaemia, undergoing allo-HCT with post-transplant cyclophosphamide in first or second complete remission, identified from the EBMT database (n=1751)
Intervention
Haploidentical transplantation: Haplo using bone marrow (Haplo-BM, n = 647) or using peripheral blood (Haplo-PB, n = 949))
Comparison
One-antigen mismatched unrelated donor transplantation (1Ag-MMUD-PB, n = 155)
Outcome
Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.28, 95% CI 1.23-4.24; HR 2.65, 95% CI 1.46-4.81, respectively). Haplo groups experienced a lower leukemia-free survival (LFS) compared to 1Ag-MMUD-PB (Haplo-BM: HR 1.51, 95% CI 1.06-2.14; Haplo-PB: 1.47, 95% CI 1.05-2.05); overall survival (OS) was also lower in Haplo-HCT (Haplo-BM: HR 1.50, 95% CI 1.02-2.21; Haplo-PB: HR 1.51, 95% CI 1.05-2.19). No differences were observed for graft-versus-host/relapse-free survival (GRFS) and relapse incidence (RI). Haplo-BM was associated with a lower risk of grade III-IV acute graft-versus-host disease (GVHD) (HR 0.44, 95% CI 0.24-0.81), while no statistical differences were observed between groups for grade II-IV aGVHD and for cGVHD.
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Impact of Early Intrapatient Variability of Tacrolimus Concentrations on the Risk of Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation Using High-Dose Post-Transplant Cyclophosphamide
Marco, D. N., Salas, M. Q., Gutiérrez-García, G., Monge, I., Riu, G., Carcelero, E., Roma, J. R., Llobet, N., Arcarons, J., Suárez-Lledó, M., et al
Pharmaceuticals (Basel, Switzerland). 2022;15(12)
Abstract
Tacrolimus (Tac) is a pivotal immunosuppressant agent used to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloHSCT). Tac is characterized by a narrow therapeutic window and a high inter-patient and intra-patient pharmacokinetic variability (IPV). Although high IPV of Tac concentrations has been associated with adverse post-transplant outcomes following solid organ transplantation, the effects of Tac IPV on alloHSCT recipients have not been determined. Tac IPV was therefore retrospectively evaluated in 128 alloHSCT recipients receiving high-dose post-transplant cyclophosphamide (PTCy) and the effects of Tac IPV on the occurrence of acute GVHD (aGVHD) were analyzed. Tac IPV was calculated from pre-dose concentrations (C(0)) measured during the first month after Tac initiation. The cumulative rates of grades II-IV and grades III-IV aGVHD at day +100 were 22.7% and 7%, respectively. Higher Tac IPV was associated with a greater risk of developing GVHD, with patients having IPV > 50th percentile having significantly higher rates of grades II-IV (34.9% vs. 10.8%; hazard ratio [HR] 3.858, p < 0.001) and grades III-IV (12.7% vs. 1.5%; HR 9.69, p = 0.033) aGVHD than patients having IPV ≤ 50th percentile. Similarly, patients with IPV > 75th percentile had higher rates of grades II-IV (41.9% vs. 16.5%; HR 3.30, p < 0.001) and grades III-IV (16.1% vs. 4.1%; HR 4.99, p = 0.012) aGVHD than patients with IPV ≤ 75th percentile. Multivariate analyses showed that high Tac IPV (>50th percentile) was an independent risk factor for grades II-IV (HR 2.99, p = 0.018) and grades III-IV (HR 9.12, p = 0.047) aGVHD. Determination of Tac IPV soon after alloHSCT could be useful in identifying patients at greater risk of aGVHD.
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Post-Transplant Cyclophosphamide for Graft vs Host Disease Prophylaxis in Multiple Myeloma Patients Who Underwent Allogeneic Hematopoietic Cell Transplantation: First Comparison by Donor Type: A Study from the Chronic Malignancies Working Party of the EBMT
Sahebi, F., Eikema, D. J., Koster, L., Kroger, N., Meijer, E., van Doesum, J. A., Rovira, M., Koc, Y., Angelucci, E., Blaise, D., et al
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND Graft-versus-host disease (GVHD), non-relapse mortality (NRM), and relapse are among major causes of treatment failure in multiple myeloma (MM) patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Use of post-transplant cyclophosphamide (PT-CY) is now a well-established and widely used method for GVHD prophylaxis after HLA haplo-identical HCT. However, the rationale for using PT-CY in the setting of matched donor transplant is less apparent, as the degree of bidirectional alloreactivity is less. OBJECTIVE Evaluate the cumulative incidence of acute and chronic GVHD, engraftment, progression-free survival (PFS), GVHD free/relapse free survival (GRFS) and overall survival (OS), as well as NRM by 2 years, using PT-CY as GVHD prophylaxis among 4 different donor types. STUDY DESIGN We analyzed PT-CY as GVHD prophylaxis in MM patients (n=295) who underwent allo-HCT using matched related (MRD, n=67), matched unrelated (MUD, n=72), mismatched related or unrelated (MMRD/MMUD, one antigen, n=27), and haploidentical (haplo; n=129) donors between 2012-2018. In addition to PT-CY, GVHD prophylaxis included calcineurin inhibitors (n=239, 81%), and mycophenolate in 184/239 (77%). OS and PFS were estimated using the Kaplan-Meier product limit estimation method, and differences in subgroups were assessed by the Log-Rank test. The cumulative incidence of relapse and non-relapse mortality were analysed together in a competing risks framework. Competing risks analyses were also applied to estimate the incidences of acute grade II-IV GVHD and limited and extensive chronic, by day 100 and one and two years, respectively. The competing events were relapse and death. Subgroup differences in cumulative incidences were assessed using Gray's test. Multivariable Cox regression was applied to investigate the simultaneous impact of multiple covariates on outcomes, when a sufficient number of patients and subsequent events were available. RESULTS Cumulative incidence of acute GVHD grade II-IV at +100 d was 30% (95%CI:25-36%), grade III-IV 9% (95%CI:5-12%), and chronic GVHD was 27% (95%CI:21-32%), limited 21% and extensive 6%, without difference among donor types. Median platelet engraftment was delayed in haplo donors (27 versus 21 d, p<0.001). Two-year OS, PFS, GRFS, and NRM were 51% (95%CI:45-58%), 26% (95%CI:20-32%), 24% (95%CI:18-30%) and 19% (95%CI:14-24%), respectively, with no significant difference between different donor types. In multivariable analyses compared to haplo, MRD was associated with significantly improved OS (HR 0.6 [0.38-0.95], p=0.029) and MUD had a significantly higher GRFS (HR 0.63 [0.42-0.97], p=0.034). There was a trend toward improved PFS with use of MUD (HR 0.69 [0.46-1.04, p=0.08]). CONCLUSION PT-CY in MM patients undergoing allo-HCT resulted in low rates of acute and chronic GVHD and led to favorable survival, especially in the matched setting.