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Total body irradiation (TBI) at myeloablative doses is superior to chemotherapy-based regimens in young patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, in elderly and unfit patients, in whom reduced-intensity conditioning (RIC) regimens are preferred, whether a TBI-based or a chemotherapy-based approach is better is unexplored. Thiotepa can be used as part of ALL conditioning regimens. The current study aimed to compare transplantation outcomes after RIC with TBI-based or thiotepa-based regimens in patients with ALL. The study cohort comprised patients aged ≥40 years undergoing allo-HSCT for ALL in first complete remission between 2000 and 2020 who received an RIC regimen containing either TBI (4 to 6 Gy) or thiotepa. We identified a total of 265 patients, including 117 who received a TBI-based RIC regimen and 148 who received a thiotepa-based RIC regimen. Univariate analysis revealed no significant differences in the following transplantation outcomes for TBI versus thiotepa: relapse, 23% versus 28% (P = .24); nonrelapse mortality, 20% versus 26% (P = .61); leukemia-free survival, 57% versus 46% (P = .12); overall survival, 67% versus 56% (P = .18); graft-versus-host disease (GVHD]/relapse-free survival, 45% versus 38% (P = .21); grade II-IV acute GVHD, 30% in both groups (P = .84); grade III-IV acute GVHD, 9% versus 10% (P = .89). The sole exception was the incidence of chronic GVHD, which was higher in the recipients of TBI-based regimens (43% versus 29%; P = .03). However, multivariate analysis revealed no differences in transplantation outcomes between the 2 groups. In patients aged ≥40 years receiving RIC, use of a thiotepa-based regimen may represent a valid alternative to TBI-based regimens, as no differences were observed in the main transplantation outcomes., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Graft failure has remained a limitation of umbilical cord blood transplantation (CBT). Here, we assessed the outcomes of patients who experienced graft failure after CBT. Inclusion criteria were patients (age ≥ 18 years) experiencing graft failure after unrelated CBT (single or double) between 2005 and 2016, for acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL), no prior allogeneic or autologous transplantation, no other stem cell product. The study included 87 patients. At 1-year, cumulative incidence of relapse and nonrelapse mortality (NRM) was 35% and 37%, respectively. One-year overall survival (OS) and progression-free survival (PFS) was 40% and 29%, respectively. Forty-six patients underwent a salvage second transplantation with 1-year and 2-year OS and PFS from second transplantation 41% and 34% for OS, and 37% and 34% for PFS, respectively. In multivariate analysis, complete remission (CR) at CBT (HR = 0.45, 95% CI 0.25-0.83, P = 0.01) and reduced-intensity conditioning (HR = 0.51, 95% CI 0.29-0.91, P = 0.023) were associated with better OS. In conclusion, in this retrospective study, we observed that approximately one-quarter of patients experiencing graft failure after CBT remained alive without relapse 2 years later., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Allogeneic hematopoietic cell transplantation is a potentially curative treatment in high-risk acute lymphoblastic leukemia (ALL). Conditioning regimens based on ≥12 Gray total body irradiation (TBI) represent the current standard in patients ≤45 years, whereas elderly patients frequently receive intermediate intensity conditioning (IIC) to reduce toxicity. To evaluate the role of TBI as a backbone of IIC in ALL, a retrospective, registry-based study included patients >45 years transplanted from matched donors in first complete remission, who had received either fludarabine/TBI 8 Gy (FluTBI8, n = 262), or the most popular, irradiation-free alternative fludarabine/busulfan, comprising busulfan 6.4 mg/kg (FluBu6.4, n = 188) or 9.6 mg/kg (FluBu9.6, n = 51). At two years, overall survival (OS) was 68.5%, 57%, and 62.2%, leukemia-free survival (LFS) was 58%, 42.7%, and 45%, relapse incidence (RI) was 27.2%, 40%, and 30.9%, and non-relapse-mortality (NRM) was 23.1%, 20.7%, and 26.8% for patients receiving FluTBI8Gy, FluBu6.4, and FluBu9.6, respectively. In multivariate analysis, the risk of NRM, acute and chronic graft-versus-host disease was not influenced by conditioning. However, RI was higher after FluBu6.4 (hazard ratio [HR] [95% CI]: 1.85 [1.16-2.95]), and LFS was lower after both FluBu6.4 (HR: 1.56 [1.09-2.23]) and FluBu9.6 (HR: 1.63 [1.02-2.58]) as compared to FluTBI8. Although only resulting in a non-significant advantage in OS, this observation indicates a stronger anti-leukemic efficacy of TBI-based intermediate intensity conditioning., (© 2023. The Author(s).)

In this registry-based study we retrospectively compared outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with acute lymphoblastic leukemia (ALL) following conditioning with total body irradiation (TBI) combined with either cyclophosphamide (Cy) or fludarabine (Flu). TBI 12 Gy + Cy was used in 2105 cases while TBI 12 Gy + Flu was administered to 150 patients in first or second complete remission. In a multivariate model adjusted for other prognostic factors, TBI/Cy conditioning was associated with a reduced risk of relapse (HR = 0.69, p = 0.049) and increased risk of grade 2-4 acute graft-versus-host disease (GVHD, HR = 1.57, p = 0.03) without significant effect on other transplantation outcomes. In a matched-pair analysis the use of TBI/Cy as compared to TBI/Flu was associated with a significantly reduced rate of relapse (18% vs. 30% at 2 years, p = 0.015) without significant effect on non-relapse mortality, GVHD and survival. We conclude that the use of myeloablative TBI/Cy as conditioning prior to allo-HCT for adult patients with ALL in complete remission is associated with lower risk of relapse rate compared to TBI/Flu and therefore should probably be considered a preferable regimen., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Allogeneic hematopoietic cell transplantation (allo-HCT) with reduced intensity conditioning (RIC) is an option for elderly patients with acute lymphoblastic leukemia (ALL). We retrospectively compared results of RIC-allo-HCT from either a matched sibling donor (MSD, n = 209) or matched unrelated donor (MUD, n = 209) with autologous (auto, n = 142) HCT for patients aged 55 years or more treated in first complete remission (CR1) between 2000 and 2018. The probabilities of leukemia-free survival (LFS) at 5 years were 34% for RIC-allo-HCT versus 39% for auto-HCT (p = 0.11) while overall survival (OS) rates were 42% versus 45% (p = 0.23), respectively. The incidence of relapse (RI) and non-relapse mortality (NRM) was 41% versus 51% (p = 0.22) and 25% versus 10% (p = 0.001), respectively. In a multivariate model, using auto-HCT as reference, the risk of NRM was increased for MSD-HCT (Hazard ratio [HR] = 2.1, p = 0.02) and MUD-HCT (HR = 3.08, p < 0.001), which for MUD-HCT translated into a decreased chance of LFS (HR = 1.55, p = 0.01) and OS (HR = 1.62, p = 0.008). No significant associations were found with respect to the risk of relapse. We conclude that for patients with ALL in CR1, aged above 55 years, auto-HCT may be considered a transplant option alternative to RIC-allo-HCT, although its value requires verification in prospective trials., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Total body irradiation (TBI) at a dose of 12 Gy combined with cyclophosphamide (CyTBI12Gy) is one of the standard myeloablative regimens for patients with acute myeloid leukemia (AML) treated with allogeneic hematopoietic cell transplantation (allo-HCT). In clinical practice, cyclophosphamide may be substituted with fludarabine (FluTBI12Gy) to reduce toxicity. We retrospectively compared outcomes of CyTBI12Gy with FluTBI12Gy for patients with AML treated in complete remission (CR) with allo-HCT from either a matched sibling or unrelated donor. Of 1684 adults who met inclusion criteria, 109 patients in each group were included in a matched-pair analysis. The cumulative incidence of relapse at 2 years was 25% in the FluTBI12Gy compared to 28% in the CyTBI12Gy group (p = .44) while non-relapse mortality (NRM) was 17% versus 19%, (p = .89) respectively. The rates of leukemia-free survival and overall survival were 65% versus 54% (p = .28) and 70% versus 60.5% (p = .17). Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) was significantly lower for FluTBI12Gy than CyTBI12Gy (16% vs. 34%, p = .005), while the incidences of grade 3-4 acute GVHD and chronic GVHD did not differ significantly. The probability of GVHD and relapse-free survival was 49% in the FluTBI12Gy and 41% in the CyTBI12Gy group (p = .17). We conclude that for patients with AML treated with allo-HCT in CR, cyclophosphamide may be substituted with fludarabine in a regimen based on TBI at a dose of 12 Gy without negative impact on the efficacy. FluTBI12Gy is associated with reduced risk of grade 2-4 acute GVHD and encouraging survival rates., (© 2023 Wiley Periodicals LLC.)

Cyclosporine A (CSA) and methotrexate (MTX) is the standard graft-versus-host disease (GVHD) prophylaxis regimen for matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). Recently, post-transplantation cyclophosphamide (PTCy) has been shown to be effective in GVHD prevention. In this registry-based study, we compared outcomes of 118 patients treated with PTCy and 1202 patients with CSA/MTX who underwent MSD allo-HCT for acute myelogenous leukemia. In a matched-pair analysis, PTCy was associated with a higher incidence of relapse at 2 years compared with CSA/MTX (41.1% versus 21.3%; P = .039). The incidences of day +180 grade II-IV acute GVHD and 2-year chronic GVHD were comparable in the PTCy and CSA/MTX arms (25.2% versus 25.4% [P = .90] and 42.6% versus 42.6% [P = .84], respectively). Similarly, 2-year leukemia-free survival (LFS; 54.4% versus 74.32%; P = .052), overall survival (OS; 70.6% versus 79.7%; P = .15), and GVHD-free relapse-free survival (GRFS; 38.1% versus 52.5%; P = .49) were not statistically different in the 2 arms. Our data show that GVHD prophylaxis with PTCy is feasible, resulting in similar incidences of GVHD, GRFS, LFS, and OS as seen with conventional CSA/MTX in patients undergoing allo-HCT from an MSD. The higher rate of relapse observed with PTCy needs further evaluation in a prospective study. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to disclose., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

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.

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., (Copyright© 2020 Ferrata Storti Foundation.)

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.

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.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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 -4 ) 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., (© 2019 American Cancer Society.)

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 ( P = .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%, P = .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; P < .001), grade III-IV aGVHD (HR, 0.21; P < .001), cGVHD (HR, 0.63; P = .02), and nonrelapse mortality (NRM) (HR, 0.54; P = .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., (© 2019 by The American Society of Hematology.)

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- versus -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- versus -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- versus -host disease were 52% and 55%, respectively. Non-adjusted overall survival, disease-free survival and non-relapse mortality rates were 55% versus 53%, 49% versus 45%, and 32% versus 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- versus -host disease was lower following antihuman T-lymphocyte immunoglobulin (hazard ratio, 0.54; P =0.010) while it did not decrease the risk of chronic graft- versus -host disease. The hazard ratios for overall survival and non-relapse mortality were 0.66 and 0.64, with P -values of 0.05 and 0.09, respectively. Antihuman T-lymphocyte immunoglobulin did not influence disease-free survival, graft- versus -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- versus -host disease without increasing the risk of relapse., (Copyright© 2019 Ferrata Storti Foundation.)

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., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

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; P < .001). In patients aged 55 to 76 years, despite lower chronic GVHD (HR, 0.42; P < .001), graft failure (14% vs 6%; P = .003), nonrelapse mortality (HR, 1.48; P = .02), and overall mortality (HR, 1.32; P = .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., (© 2018 by The American Society of Hematology.)

Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with higher risk myelodysplastic syndrome (MDS), but the choice of the optimal alternative stem cell source is still a subject of debate in patients lacking an HLA-matched sibling donor. Here, we report on a large series of patients with MDS (N = 631) transplanted either with mobilized peripheral stem cells (PBs) from unrelated donors (n = 502) or with umbilical cord blood transplant (UCB, n = 129) as alternative grafts after reduced-intensity conditioning. Neutrophil engraftment was higher after PB (98% versus 78%, P < .0001). Acute graft-versus-host disease (GVHD) was similar after PB (31%) and UCB (29%), and chronic GVHD incidence was higher after PB (41% versus 23%). Two-year nonrelapse mortality was lower after PB (31% versus 42% P = .03). There was a better overall survival (OS) and disease-free survival (DFS) after PB (49% ± 2% versus 30% ± 4%, P < .0001 and 44% ± 2% versus 28% ± 4%, P < .0001). Multivariate analysis confirmed the advantage of PB for treatment-related mortality, OS, and DFS, whereas relative risk of chronic GVHD was similar. A multivariate analysis comparing PB from a 10/10 HLA-matched donor, PB from a 9/10 HLA-matched donor, and UCB showed an advantage on treatment-related mortality, DFS, and OS only in 10/10 PB. We conclude that in MDS patients lacking an HLA-matched sibling donor, PB from a 10/10 HLA-matched unrelated donor is the preferred source of hematopoietic stem cells. HLA-mismatched unrelated donor or cord blood seem to give similar inferior results except for neutrophil engraftment, which is delayed after UCB., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

This retrospective study analyzed the impact of demographic and transplantation variables on outcomes of 1108 patients who have undergone allogeneic hematopoietic stem cell transplantation after reduced intensity conditioning (RIC HSCT) for hematological malignancies and were reported to the Société Française de Greffe de Moelle et de Thérapie Cellulaire registry between November 1994 and December 2004. Only 442 patients (40%) were in complete remission (CR) at time of transplantation. Peripheral blood stem cells were used in the majority of patients (n = 878; 79%), 255 patients received fludarabine and low-dose total body irradiation, while 465 patients (42%) fludarabine and busulfan with rabbit anti-thymocyte globulins (ATG). The impact of demographic and transplant variables was studied on overall (OS) and event-free survival (EFS) in univariate and multivariate analysis. With a median follow-up of 21 months, 3-year probability of OS and EFS was 42% and 30%, respectively, and treatment-related mortality was 15% at 2 years. The multivariate analysis showed a significant negative impact on OS and EFS of the absence of CR status before transplantation; conditioning regimen, including >10 mg/kg ATG; and minor ABO incompatibility. In conclusion, this study highlights the major impact on RIC HSCT outcome of disease status before transplantation, ATG dose and ABO incompatibility.

The use of peripheral blood stem cells (PBSCs) is rapidly growing in the allogeneic transplantation setting as an alternative to bone marrow (BM). We previously reported a higher incidence of chronic graft-versus-host disease (cGVHD) associated with allogeneic PBSC transplantation in a randomized trial. In this follow-up report, we analyzed the evolution of cGVHD in the patients (n = 101) enrolled on this study. At a median follow-up of 45 months (range, 31-57 months), we found that the 3-year cumulative incidence of cGVHD was 65% (95% confidence interval [CI] 51%-78%) in the PBSC group and 36% (95% CI 23%-49%) in the BM group (P =.004). We also found that extensive cGVHD was more frequent in the PBSC group (44% [95% CI 30%-58%] vs 17% [95% CI 7%-27%]; P =.004). The prevalence of cGVHD was always higher in the PBSC arm. Ocular involvement was more frequent in PBSC recipients (P =.02). Cutaneous and liver involvement was similar among BM and PBSC recipients. Chronic GVHD required multiple courses of immunosuppressive therapy in addition to cyclosporine and corticosteroids during longer periods (P =.03). Altogether, this translated into longer periods of hospitalization after transplantation in the PBSC group (P =.04). Finally, we also confirm that cGVHD after PBSC transplantation is associated with an antileukemic effect that is at least as potent as after BM. However, to date, this has not translated into a survival difference, possibly due to the early-stage leukemic status of these patients or to the relatively small size of the study population.