Matched Unrelated Research Articles

The effects of substituting cladribine for fludarabine on outcomes of a reduced intensity conditioning regimen.

e18518 Background: Drug shortages may be encountered especially in times of pandemics and war. The extrapolation of data focusing on different diseases may provide clinical clues for substituting two chemotherapeutic drugs of the same class. The substitution of cladribine for fludarabine in a reduced intensity conditioning (RIC) regimen composed of fludarabine, melphalan and total body irradiation (TBI) may yield similar side effect profile and outcomes. Methods: Consecutive patients undergoing an allogeneic stem cell transplant in our center between November 2019 to December 2022 were included. Within this period cladribine had to be substituted for fludarabine during a drug shortage. All patients received intravenous melphalan 75 mg/m2/day on day -2, and 200 cGy TBI on day -1. The regimen included either subcutaneous cladribine 10 mg/m2/day on days -5 to -2, or intravenous fludarabine 40 mg/m2/day on days -5 to -2. Graft versus host disease (GvHD) prophylaxis included a calcineurin inhibitor (CNI) + mycophenolate mofetil (MMF) for matched related donor transplants; and post-transplant cyclophosphamide + CNI + MMF for matched unrelated (MUD) and haploidentical donors. The distributions and medians of studied parameters in two cohorts were compared with non-parametric methods. Overall survival (OS), progression-free survival (PFS) and transplant-related mortality (TRM) were estimated by the Kaplan-Meier Method. The cut-off for statistical significance was defined as p<0.05. Results: A total of 70 patients (27 in cladribine and 43 in fludarabine cohort) were included. Median age was 59 (22 to 76) and 64.3% constituted males. Median follow-up was 10.2 months (0.1 to 44.7). Acute leukemia diagnosis, intermediate to high disease risk index (DRI) and intermediate to high Charlson comorbidity index (CCI) constituted 45.7%, 60.0% and 58.1% respectively. Haploidentical donors were used in 28.6%. The distribution of gender, diagnosis, DRI and CCI scores, donor type, total CD34 dose given, panel reactive antibody (PRA) positivity were similar. Median days to neutrophil engraftment was shorter with fludarabine (19 vs 16, p=0.01), however, median duration of in-unit stay was similar (27 vs 28 days, p=0.73). TRM, nausea and acute GvHD frequency was lower with cladribine (p=0.35, p=0.001 and p=0.02, respectively). Typhilitis and perianal infections were more common with cladribine (p=0.07 and p=0.04, respectively). OS and PFS were similar (p=0.81 and p=0.66, respectively). When cladribine was compared to fludarabine on day +90, OS was 78,0% (95% CI: 62.3-93.7) vs 65,0% (95% CI: 51.3-78.7); PFS was 70.0% (95% CI: 52.4-87.6) vs 65.0% (95% CI: 51.3-78.7); TRM was 19.0% (95% CI: 3.3-34.7) vs 24.0% (95% CI: 10.3-37.7). Conclusions: Cladribine may be safely constituted for cladribine in a RIC regimen and may yield similar, even some favorable, outcomes when compared to fludarabine.

Post-Transplant Cyclophosphamide versus Anti-Thymocyte Globulin in Patients with Hematological Malignancies Treated with Allogeneic Hematopoietic Stem Cell Transplantation from Haploidentical and Matched Unrelated Donors: A Real-Life Experience.

Background: Post-transplant cyclophosphamide (PTCY) is widely used as graft versus host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplant (HSCT) recipients, with reported clinical benefits in patients who underwent transplant from a matched unrelated donor (MUD). However, real-life data on clinical efficacy and safety of PTCY in haploidentical and MUD transplantations are still poor. Methods: In our real-life retrospective observational study, we included a total of 40 consecutive adult patients who underwent haploidentical or MUD HSCT for various hematological malignancies and who received PTCY (n = 24) or ATG (n = 16) as GvHD prophylaxis at Hematology Units from hospitals of Salerno and Avellino, Italy, and clinical outcomes were compared. Results: We showed protective effects of PTCY against disease relapse with the relapse rate after transplantation of 16% versus 50% in the ATG arm (p = 0.02). All-cause mortality was lower (36% vs. 75%; p = 0.02) and the 2-year overall survival was slightly superior in patients administered PTCY (61% vs. 42%; p = 0.26). Conclusions: We support the use of PTCY, even in a real-life setting; however, the optimization of this protocol should be further investigated to better balance relapse prevention and GvHD prophylaxis.

Lower incidence of grade II-IV acute Graft-versus-Host-Disease in pediatric patients recovering with high Vδ2+ T cells after allogeneic stem cell transplantation with unmanipulated bone marrow grafts: a prospective single-center cohort study.

Gamma delta (γδ) T cells represent a minor fraction of human T cell repertoire but play an important role in mediating anti-infectious and anti-tumorous effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a prospective study to analyze the effect of different transplant modalities on immune reconstitution of γδ T cells and subsets. CD3, CD4 and CD8 T cells were analyzed in parallel. Secondly, we examined the impact of γδ T cell reconstitution on clinical outcomes including acute Graft-versus-Host-Disease (aGvHD) and viral infections. Our cohort includes 49 pediatric patients who received unmanipulated bone marrow grafts from matched unrelated (MUD) or matched related (MRD) donors. The cohort includes patients with malignant as well as non-malignant diseases. Cell counts were measured using flow cytometry at 15, 30, 60, 100, 180 and 240 days after transplantation. Cells were stained for CD3, CD4, CD8, CD45, TCRαβ, TCRγδ, TCRVδ1, TCRVδ2, HLA-DR and combinations. Patients with a MRD showed significantly higher Vδ2+ T cells than those with MUD at timepoints +30, +60, +100 (p<0.001, respectively) and +180 (p<0.01) in univariate analysis. These results remained significant in multivariate analysis. Patients recovering with a high relative abundance of total γδ T cells and Vδ2+ T cells had a significantly lower cumulative incidence of grade II-IV aGvHD after transplantation (p=0.03 and p=0.04, respectively). A high relative abundance of Vδ2+ T cells was also associated with a lower incidence of EBV infection (p=0.02). Patients with EBV infection on the other hand showed higher absolute Vδ1+ T cell counts at days +100 and +180 after transplantation (p=0.046 and 0.038, respectively) than those without EBV infection. This result remained significant in a multivariate time-averaged analysis (q<0.1). Our results suggest a protective role of γδ T cells and especially Vδ2+ T cell subset against the development of aGvHD and EBV infection after pediatric HSCT. Vδ1+ T cells might be involved in the immune response after EBV infection. Our results encourage further research on γδ T cells as prognostic markers after HSCT and as possible targets of adoptive T cell transfer strategies.

Fludarabine and Melphalan Reduced Toxicity Versus a Myeloablative Fludarabine and Busulfan Conditioning Regimen for Acute Myeloid Leukemia

Introduction: The optimal induction regimen for an allogeneic hematopoietic cell transplant (allo-HCT) for a young adult patient diagnosed with acute myeloid leukemia (AML) remains to be defined. Among reduced intensity regimens (RIC), retrospective registry data from both CIBMTR and EBMT would suggest that a Fludarabine / Melphalan (Flu/Mel) regimen was superior to a Fludarabine / Busulfan x 2 (Flu/Bu2) regimen. The need for a myeloablative conditioning regimen over a RIC has been evaluated in at least six randomized clinical trials (RCT), and the results have yet to be uniform. Published meta-analysis suggests equipoise. The studies are further limited by including a heterogenous group of conditioning regimens, especially in the reduced intensity arm; they all come from developed countries, a mix of AML and MDS in most studies, and variation in age groups enrolled in them. In India and developing countries, there remain significant challenges with multi-drug resistant infections, financial constraints, and challenges with intensive care support. We hypothesize that in this setting, a reduced toxicity regimen, such as a combination of Fludarabine with Melphalan (140 mg/m 2) (Flu/Mel), may be preferable to a myeloablative regimen. Methods: A single-center retrospective analysis was undertaken to study the impact of a reduced toxicity Flu/Mel regimen versus a myeloablative Fludarabine combined with Busulfan (130 mg/m 2/day x 4 days) regimen (Flu/Bu4). All consecutive patients in all age groups with a diagnosis of AML who underwent an allo-HCT between Jan 2005 and Dec 2021 were included in this analysis. The conditioning regimen used was as per physician discretion with a broad guideline within the department to use a myeloablative Flu/Bu4 regimen in a young fit patient with high-risk features such as high-risk ELN at diagnosis, CR2, and beyond, or requiring more than one cycle of induction chemotherapy to achieve a complete remission (CR). Results: 439 patients underwent an allo-HCT for a diagnosis of AML at our center in the given time. The median age was 33 years (range: 1 - 63), and there were 267 (60.8%) males. The transplants were done in CR1 in 236 (54%), CR2 in 90 (20.5%), CR3 in 13 (3%), and in relapsed/refractory or with active disease in 100 (22.8%). The majority were matched sibling/related donors (MRD) in 284 (64.7%), followed by matched unrelated (MUD) in 75 (17.1%) and haploidentical in 80 (18.2%). The conditioning regimen used was Flu/Mel in 170 (38.7%), Flu/Bu4 in 185 (42.1%), and a mix of other regimens in 84 (19.1%). At an actuarial median follow-up of 4 years, the overall survival (OS) and event-free survival (EFS) of the entire cohort were 40.8% ± 3.0% and 38.6% ± 3.0%, respectively. The EFS of cases in CR1, CR≥2, and in relapsed/refractory/active disease were 47.7% ± 3.8%, 45.0% ± 5.5%, and 12.3% ± 3.6%, respectively. The baseline characteristics and clinical outcome of cases that received a Flu/Mel condition versus Flu/Bu4 conditioning are summarized in Table 1. In summary, baseline characteristics were comparable between the two groups, except that significantly more cases underwent a haploidentical transplant in the Flu/Bu4 group. In contrast, in the Flu/Mel group, there were significantly more cases in CR1, and the median age was also significantly older. The 5-year KM EFS of the Flu/Mel and Flu/Bu4 cohort was 51.7±3.9% and 43.9±3.9% (P-value = 0.297), respectively (Figure 1). On univariate analysis, only CR1 status before transplant and the presence of chronic GVHD impacted EFS positively, and on multivariate analysis, only CR1 status affected EFS. Conclusion: In conclusion, in one of the most extensive retrospective studies comparing a uniform reduced toxicity conditioning regimen with Flu/Mel versus a standard myeloablative Flu/Bu4 conditioning regimen, we find no significant advantage of Flu/Bu4 over a Flu/Mel conditioning regimen.

Comparing Older Matched Related to Younger Matched Unrelated Donors in Acute Myeloid Leukemia in Remission Using Post-Transplant Cyclophosphamide

Backgroud. Over the past 25 years, the landscape of allogeneic stem cell transplantation (allo-SCT) changed from being rarely performed in patients 50 years or older to accounting for a little less than half of the transplantations reported in USA and Europe. Older patients will on average have older matched related siblings (MRD) being considered as donors with issues such as comorbidities, risk of clonal haematopoiesis of indeterminate potential, and impaired immune and regenerative potential of stem cells. Although younger HLA-matched unrelated donors (MUD) are an important alternative in this context, it remains unclear whether the use of MUD is associated with better outcomes. This is especially true in the context of post-transplant cyclophosphamide (PTCy) as graft-versus-host disease (GvHD) prophylaxis. Methods. The aim of this study was to compare the graft-relapse-free survival (GRFS) for patients diagnosed with acute myeloid leukemia (AML) in first complete remission (CR1), aged 50y or more, and having received a first allo-SCT from a 10/10 MUD younger than 40y or a MRD older than 50y using PTCy for in-vivo T-cell depletion. All transplants were performed between 2015-2021 at the EBMT centres. Results. A total of 410 consecutive patients were included, 172pts receiving a MRD, 238pts transplanted from a MUD. All patients with detailed conditioning regimen dosages were classified according to the transplant conditioning intensity (TCI) score in low (1-2), intermediate (2.5-3.5), high (4-6). TCI-score was available for 345 patients and was as follows: low in 53pts (36.8%), intermediate in 79pts (54.9%) and high in 12pts (8.3%) for MRD, low in 91pts (45.3%), intermediate in 93pts (46.3%) and high in 17pts (8.5%) for MUD (p=0.26). Only patients with available TCI-score were analysed. In univariate analysis the 2-year GRFS was 58% (49.8-65.3%) for TCI intermediate-high and 43.1% [34.3-51.5] for TCI low (p=0.005). In TCI-score intermediate-high non-relapse mortality (NRM) wasn't higher compared to TCI-score low (12.7% [12.2-24] vs 13.7% [8.4-20.3], p=0.53) but relapse incidence (RI) was lower (17.7% [12.2-24] vs 33.2% [25.1-41.5], p=0.003). As a strong interaction between TCI-score and type of donor was found, we compared transplant outcomes between MRD and MUD separately for TCI-score low and TCI-score intermediate-high. In TCI-score low, 2-year GRFS was 44.4% [33.5-54.8] for MUD and 40.9% [26.4-54.9] for MRD (p=0.83) (Figure 1A). In multivariable analysis (MVA) type of donor was not a risk factors for neither GRFS (HR 0.98, CI: 0.57-1.69; p=0.95) nor for any other transplant outcome. In TCI-score intermediate-high, 2-year GRFS was 67.2% [55.8-76.2] for MUD and 46.1% [34.4-57.1] for MRD (p=0.001) (Figure 1B). In MVA MUD were associated to better GRFS (HR 0.41, CI: 0.24-0.7; p=0.001), lower NRM (HR 0.19, CI: 0.07-0.55; p=0.002) and lower RI (HR 0.32, CI: 0.14-0.73; p=0.007) without advantages in terms of neither aGvHD nor cGvHD. Conclusions. In patients with AML in CR1, aged 50y or more and receiving a conditioning regimen with TCI-score ≥ 2.5 in the PTCy setting, a MUD younger than 40y is associated to longer GRFS, lower NRM and lower RI compared to a MRD older than 50y. For patients receiving regimens with TCI-score low transplant outcomes are independent on the type of HLA-matched donor.

Graft Versus Host Disease Prophylaxis with Tacrolimus, Sirolimus and MMF in Patients Undergoing Reduced Intensity Conditioning Allogeneic Transplantation

I ntroduction GvHD remains the leading cause of toxic morbidity and mortality (NRM) after allo-HSCT. Different prophylaxis schemes have been developed in the context of reduced intensity conditioning (RIC). In 2019, the multicenter phase 3 trial NCT01231412 compared GvHD prophylaxis based on the calcineurin inhibitor (CNI) CSA plus MMF with (experimental arm) or without (control arm) sirolimus. The triple combination was associated with a lower risk of aGvHD and longer survival and, in the authors' opinion, could constitute a new standard (Sandmaier, Lancet Oncol 2019). We present the largest real-world experience to date with the triple prophylaxis scheme in the context of allo-HSCT with RIC from matched-related (MRD), matched-unrelated (MUD) and mismatched URD (mmURD). Material and Methods Prospective study of 159 consecutive patients receiving an allo-HSCT after RIC between 09/2019 and 12/2022 at two centers using the tacro/siro/MMF as GvHD prophylaxis. The primary endpoint was the cumulative incidence of aGvHD grades 2-4. As secondary variables: cGvHD at 1 and 3 years, NRM at +100, +1 year and overall NRM, OS at 1 and 3 years, PFS at 1 and 3 years and GRFS at 1 and 3 years. Results Baseline characteristics are shown in Table 1. Note the high percentage of patients with high/very high rDRI or HCT-CI of 3+. In 38.4% an URD was used as source of progenitor cells and in 20.8% it was a MMURD. The median follow-up was 20 months (3-40). There were 4 (2.5%) graft failures (2 of them secondary). Median neutrophil and platelet engraftment was 16 days (3-175) and 12 days (7-210). The risk of relapse was 31% and 35% at 1 and 3 years. NRM at day +100, + 1 year and overall NRM was 4.4%, 8.17% and 9.4%. The causes of NRM were GvHD +/- infection in 73%, with other causes being TMA (n=1) and SOS (n=1). The cumulative incidence (CI) of grades 2-4 aGvHD 2-4 at day +100 and +180 was 29.7% and 32.3%, including 40% of upper gastrointestinal tract involvement which resolved with topical treatment. The CI of grades 3-4 aGvHD at day +100 and +180 was 12.8% and 16% (3.14% grade 4). The CI of cGvHD at 1 and 3 years was 21.5% and 51.2% and for moderate/severe it was 13.9% and 36.6%. OS at 1 and 3 years was 70.3% and 61%. Median PFS was 35 months, with 1- and 3-year PFS of 60% and 49%. The GRFS at 1 and 3 years was 44% and 32%. The risk of grades 2-4 aGvHD was significantly higher among patients receiving allo-HSCT from MMURD (at d+100 and +180, 35.4% and 39.9%) vs matched donors (at d+100 and +180, 55.5% and 61%, p=0.04). The same variable also influenced on OS (at 1 and 3 years 73.3% vs 64.6% and 57.6% vs 37.8% for matched vs mismatched donors, respectively; p=0.013) (Figure 1). On the other hand, low and intermediate DRI patients had a significantly better OS as compared to high/very high rDRI patients (at 1 and 3 years 80.8% and 80.8% for low vs 86.7% and 78.3% for intermediate vs 56.9% and 55.1% for high and very high; p=0.013) (Figure 1). Conclusions Triple prophylaxis with Tacro-Siro-MMF shows excelent results in terms of NRM, GvHD and survival in a high-risk and elderly population in the context of allo-HSCT from matched-related (MRD) and matched-unrelated (MUD) donors. The subgroup of patients receiving allo-HSCT from MMURD showed a high incidence of overall and grade 3-4 aGvHD with impact on OS, being a group that will probably benefit from other prophylaxis strategies.

Choosing Between Older Matched Sibling Donor and Younger Matched Unrelated Donor in Allogeneic Hematopoietic Cell Transplantation: Comparison of Clinical Outcomes in Acute Myeloid Leukemia and Myelodysplastic Syndrome

The choice between an older matched sibling donor (MSD) and a younger matched unrelated donor (MUD) in allogeneic hematopoietic cell transplantation (HCT) remains a subject of ongoing debate. In this single-center retrospective study of 377 patients who received peripheral blood stem cell (PBSC) transplants for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), we compared outcomes of 85 patients who received grafts from MSDs age >60 years and 292 patients who received grafts from MUDs age <30 years. Compared to recipients of MSD transplants, recipients of MUD transplants were younger and more likely to receive dual T cell depletion (TCD), a higher CD34+ cell dose, and a fresh graft. Recipients of MSD transplants were maintained on immunosuppressive therapy longer than those who received MUD grafts. We found no differences in overall survival, relapse-free survival, graft-versus-host disease (GVHD)-free and relapse-free survival, nonrelapse mortality, relapse, engraftment, graft failure, and acute GVHD between recipients of MSD grafts and recipients of MUD grafts. We report a higher 30-day incidence, but not 1-year incidence, of bloodstream infections among recipients of MUD transplants compared to subjects who received their grafts from a MSD. The incidence of moderate-severe chronic GVHD was higher in MSD graft recipients compared with MUD graft recipients in univariate analysis, but not in multivariate analysis. Although this difference could reflect the greater use of dual TCD, known to be associated with very low rates of chronic GVHD in MUD transplant recipients, the incidence of moderate-severe chronic GVHD was no different between MSD and MUD transplant recipients following propensity score matching, suggesting that other variables could be responsible. Taken together, our data suggest that in patients with AML or MDS who receive PBSC transplants, such factors as convenience, ease of access, and costs should be considered when selecting an older MSD over a younger MUD.

Younger Matched Unrelated Donors Confer Decreased Relapse Risk Compared to Older Sibling Donors in Older Patients with B Cell Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

Although allogeneic hematopoietic cell transplantation (alloHCT) offers cure for older patients with acute lymphoblastic leukemia (ALL), disease relapse remains a major issue. Whether matched sibling donors (MSDs) are still the preferred donor choice compared to younger matched unrelated donors (MUDs) in the contemporary era of improved transplantation practices remains unknown. This retrospective cohort registry study queried the Center for International Blood and Marrow Transplant Research (CIBMTR) database in patients with B cell ALL (B-ALL) age ≥ 50 years undergoing alloHCT from older MSDs (age ≥ 50 years) or younger MUDs (age ≤ 35 years) between 2011 and 2018. The study included common allograft types, conditioning regimens, and graft-versus-host disease (GVHD) prophylaxis strategies. The primary outcome was relapse risk, and secondary outcomes included nonrelapse mortality (NRM), GVHD, leukemia-free survival (LFS), and overall survival (OS). Among 925 eligible patients in the study cohort, 386 underwent alloHCT with an older MSD (median donor age, 58 years) and 539 underwent alloHCT from a younger MUD (median donor age, 25 year). In multivariable analysis, younger MUDs conferred a significantly decreased risk of relapse (hazard ratio [HR], .68; P=.002) compared with older MSDs. The adjusted cumulative incidence of relapse at 5 years was significantly lower with younger MUDs than with older MSDs (26% versus 37%; P=.001). Younger MUDs were associated with a greater riskof chronicGVHD compared to older MSDs (HR, 1.33; 95% confidence interval [CI], 1.10 to 1.61; P=.003). Compared to older MSDs, younger MUDs conferred an increased NRM (HR, 1.38; P=.02) and higher adjusted cumulative incidence of NRM at 5 years (31% versus 22%; P=.006). There were no differences in post-alloHCT OS or LFS rates between younger MUDs and older MSDs (OS: HR, 1.09; [P=.37]; LFS: HR, .95 [P=.57]). The use of younger MUDs could be considered as a possible way to prevent relapse after alloHCT in older adults with ALL. Combining the use of younger MUDs with improved strategies to reduce GVHD merits further exploration to improve outcomes.

314 - Adenovirus Infection Following Hematopoietic Cell Transplantation (HCT) with Post-Transplant Cyclophosphamide (PTCy): Outcomes in Haploidentical Versus Matched or Mismatched Unrelated Donor (MUD/ MMURD) Allografts

314 - Adenovirus Infection Following Hematopoietic Cell Transplantation (HCT) with Post-Transplant Cyclophosphamide (PTCy): Outcomes in Haploidentical Versus Matched or Mismatched Unrelated Donor (MUD/ MMURD) Allografts

27 - Comparison of Allogeneic Hematopoietic Cell Transplantation Outcomes from Younger Matched Unrelated Donor Versus Older Sibling Donor for Older Adults with AML

27 - Comparison of Allogeneic Hematopoietic Cell Transplantation Outcomes from Younger Matched Unrelated Donor Versus Older Sibling Donor for Older Adults with AML

28 - Younger Matched Unrelated Donors Confer a Decreased Relapse Risk As Compared to Older Sibling Donors for Adult B-Cell ALL Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

28 - Younger Matched Unrelated Donors Confer a Decreased Relapse Risk As Compared to Older Sibling Donors for Adult B-Cell ALL Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

Allogeneic Hematopoietic Cell Transplantation in Patients with Therapy-Related Myeloid Neoplasm Following Treatment for Lymphoma: A Study of the Chronic Malignancies Working Party of the EBMT

Introduction: Therapy-related myeloid neoplasms (t-MNs) represent group of myeloid neoplasms arising after treatment for an antecedent cancer or autoimmune disease and historically present a dismal prognosis. Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for t-MN. The Chronic Malignancies Working Party of EBMT previously reported outcomes for t-MN following breast cancer treatment demonstrating comparable outcomes to de novo disease and the crucial role of oncological surveillance due to risk of relapse of primary cancer. In this retrospective registry-based study, we analyzed the outcomes and complications of patients with t- MN arising secondary to lymphoma treatment who underwent allo-HCT. Methods: Patients ≥18 years old receiving a first allo-HCT for t-MN [either therapy-related Myelodysplastic syndrome (t-MDS) or t-Acute myeloid leukemia (t-AML)] between 2006 and 2017 were included in this analysis. Both t-MN arising after completion of treatment for Hodgkin and Non-Hodgkin Lymphoma were included. Results: In the EBMT registry, we identified 378 patients from 47 centers. t-MDS was the indication for allo-HCT in 222 (59%) and t-AML in 156 patients (41%), respectively, with a median age at allo-HCT of 58 years and males representing 62% of cases. Most of the patients were previously treated for Follicular Lymphoma (22%), followed by Hodgkin's Lymphoma (22%) and Diffuse large B-cell Lymphoma (16%). Autologous HCT was a prior line of therapy in 38% of cases, and at the time of allo-HCT 15% of lymphomas were not in complete remission (CR). For t-MN, CR was recorded at the time of allo-HCT in 46% of cases, with a Karnofsky status >80 in 66%. The conditioning regimen was reduced intensity in 70% of patients, 22% received TBI and 65% received T-cell depletion. Stem cell source was peripheral blood in 90% of cases. Donor was matched related (MRD) in 26%, matched unrelated (MUD) in 46%, mismatched related (MMRD) in 4% of cases, and mismatched unrelated (MMUD) in 20% of cases, respectively. Median follow-up was 72 months, and the 5-year overall survival (OS) was 32%. In univariate analysis, OS was worse for patients transplanted for t-MDS (26 vs 41% for t-MDS vs t-AML, p=.032), not being in remission for t-MN at the time of allo-HCT (24% vs 38% for CR vs 34% for untreated, p=.013), and patients with a longer interval from lymphoma diagnosis to allo-HCT (23% for >10 years vs 37% for 5-10 years vs 36% <5 years, p=.028). Five-year t-MN progression-free survival (PFS) was 28%: patients with active t-MN at allo-HCT presented with lower PFS (33% vs 20% for CR vs 31% for untreated, p=.003) as did patients with t-MDS (22% vs 36% for t-AML, p=.022). t-MN Relapse incidence (RI) and Non-relapse mortality (NRM) at 5 years were 35% and 37%, respectively. Uncontrolled t-MN was associated with higher RI (42% vs 35% for CR vs 25% for untreated, p=.025); having an MRD was associated with a worse RI (48%, 33%, 25%, 31% for MRD, MUD, MMRD, and MMUD, p=.009), but to a significantly lower NRM (21%, 35%, 47%, 52% for MRD, MUD, MMRD, and MMUD, p<0.001). A higher NRM was observed in patients older than 60 years (44% for >60 years vs 34% for 50-60 years vs 27% for <50 years, p=.034) and in those with heavily pretreated lymphoma, (32% for 1st CR vs 40% for 2nd CR vs 61% for ≥3rd CR vs 45% for not in CR, p=.028). Acute grade II-IV GVHD occurred in 33% of patients (14% grade III-IV), with a 12-months incidence of chronic GVHD of 32% (18% of extensive grade). By 5 years post allo-HCT, the relapse incidence of lymphoma was 3% at 60 months, while the rate of secondary malignancies was 8%. On multivariable analysis, compared to t-MN in CR, uncontrolled t-MN was associated with significantly worse OS, PFS, and NRM. Age was correlated with better OS, PFS, and higher NRM (all p-values<0.04). MRD was associated with higher RI (p=.03) and worse NRM (p=.02). Conclusions: This analysis shows encouraging results for patients treated with allo-HCT for t-MN arising secondary to lymphoma treatment, however significant rates of NRM and relapse remain of concern. Lymphoma recurrence represents a rare event, but when considered together with the relatively high rate of secondary malignancies (8%) necessitates vigilance. Of note, our cohort was exposed to conventional chemotherapeutic agents for lymphoma treatment, and further efforts should explore supplementary variables in addition to the impact of novel therapies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Frequency and Clinical Significance of Mixed T-Cell Chimerism Following Myeloablative Busulfan and Cyclophosphamide Conditioning in HLA -Matched Donor Transplants for Myeloid Malignancies: An Analysis of 179 Patients Transplanted at a Single Center

Myeloablative busulfan and cyclophosphamide (BuCy2) is one of the most used preparative regimens for allogeneic hematopoietic cell transplantation for myeloid malignancies from HLA-identical (MRD) and 8 of 8 HLA-A, B, C and DRB1 allele matched unrelated (MUD) donors. However, mixed T-cell chimerism may be relatively common during the early post-engraftment phase using this regimen. The significance of early incomplete donor T-cell chimerism following BuCy2 allotransplants with respect to post-transplant outcomes is unclear. Methods: We analyzed 179 consecutive patients who underwent allotransplants for myeloid malignancies using myeloablative BuCY2 conditioning at our center. Cyclophosphamide was administered at 60mg/m2/d x 2 and busulfan was administered over four days with pharmacokinetically targeted exposure (usually 4.9 mgxhr/L) based on test dosing. Tacrolimus/methotrexate was used for GVHD prophylaxis. Uniform institutional supportive care protocols were employed for all patients. Lineage specific chimerism on T-cell (CD3) and myeloid (CD33) peripheral blood (PB) cells separated using immunomagnetic beads was performed monthly through d 100 following transplant. Patients with < 50% donor CD3 chimerism on d30 were scheduled to receive low dose DLI if available (starting at 5-10 x 10e5 CD3 cells /kg) while maintaining therapeutic tacrolimus levels. No intervention was performed if d30 donor CD3 chimerism was > 50%. Outcomes were analyzed using data extracted from our institutional database where information had been prospectively entered. GVHD diagnosis and grading were determined by a single dedicated practitioner. Results: Patient characteristics were: median age 50 (18-66), male 51%; diagnosis AML (65%), CML (23%) MDS/MPS (12%); MRD (52%) MUD (48%); graft source- PBSC 81%, BM18%, both 1%; DRI - low 12%, intermediate 57%, high 25%, very high 6%; donor CMV pos 51%, neg 49%; year of transplant- 2004-2012 (35%), 2013-2016 (32%) 2017-2021(33%). Median follow-up for surviving patients was 84 months (6-213). Kaplan-Meier (K-M) estimates for survival and relapse-free survival at 5 years for all patients were 66% (95%CI 58-73%) and 59% (51-66%). Median (range) donor chimerism on d 30 for CD3 cells was 80% (6-100%) and for CD33 cells was 100% (84-100%). Median CD3 chimerism on d 60, d 100 and d 180 were 86%(7-100%), 91% (8-100%) and 95% (12-100%) respectively. Twenty-four patients (13%) had CD3 <50% on d30 of which 9 received DLI. On multiple regression modeling (Table1) the following factors were associated with higher d 30 CD3 chimerism - diagnosis (AML vs other) (difference 0.104, p=0.001), DRI (high/v.high vs low/intermediate)(diff 0.070, p=0.03) and graft CD3 dose (>15.5x 10e7/kg vs < 15.5) (diff 0.105, p<0.001) For patients who had > 80% vs <80% donor CD3 chimerism on d 30, 5-year K-M estimates of survival and RFS were 56% vs 76% (p=0.003) and 54% vs 64% (p=0.16). Five-year cumulative incidences of NRM and relapse were 20% vs 8% (p=0.010) and 26% vs 28% (p=0.85). Cumulative incidences of grade 2-4 and grade 3-4 acute GVHD at 6 months were 49% vs 27% (p=0.002) and 20% vs 4% (p=0.001) respectively. Cumulative incidences of moderate to severe and severe chronic GVHD at 3 years were 81% vs 64% (p=0.017) and 53% vs 34% (p=0.008). On a Cox proportional-hazards model adjusting for significant patient, disease and transplant covariates, d 30 CD3 chimerism > 80% was associated with a significantly higher risk of NRM (HR 3.42, p=0.007), aGVHD gd 2-4(HR1.79, p=0.013), aGVHD gd 3-4 (HR 2.66, p=0.008) and severe cGVHD (HR 1.84, p=0.011). However, d 30 CD3 chimerism was not significantly associated with relapse, survival and relapse-free survival (Fig 1). Conclusions: These data suggest that while pharmacokinetically-targeted BuCy2 as administered is almost always myeloablative (CD33 chimerism 100%), early mixed T-cell chimerism is relatively common (CD3 chimerism < 80% in 50% of patients). d30 CD3 chimerism ≥80% is not associated with lower relapse rates or better survival outcomes, but is associated with higher rates of acute and chronic GVHD. No intervention to improve CD3 chimerism appears necessary for patients with d 30 CD3 chimerism between 50 and 80%. Patients with ≥ 80% CD3 chimerism at d 30 may benefit from more aggressive measures to prevent acute and chronic GVHD Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Allogeneic but Not Autologous Stem Cell Transplantation Improves Outcome in HTLV-1-Associated North American Adult T-Cell Leukemia/Lymphoma

Background: Adult T-cell leukemia/lymphoma (ATLL) is a rare mature T-cell malignancy driven by the human T-cell lymphotropic virus type I (HTLV-1) that remains challenging to treat and is associated with a dismal prognosis. While some reports have shown encouraging results with allogeneic stem-cell transplantation (allo-SCT), data remains scarce and mostly limited to Japanese patients. Patients and Methods: This is a retrospective single center analysis with 100 HTLV-1-associated North American ATLL patients. Variables collected included age, sex, ethnicity, CMV/HTLV1 serologies, karnofsky performance score (KPS), diagnosis date, disease subtype, number of prior therapy lines, transplant type, status at transplant, transplant date, prior SCT, donor sex, CMV/HTLV1 serologies, stem cell source, donor type, in-vivo T-cell depletion, engraftment, conditioning regimen, GVHD prophylaxis, maximum acute and chronic GVHD grade, relapse date when applicable, and main cause of death. The Kaplan-Meier method was used to calculate overall survival (OS) and progression-free survival (PFS). Cumulative incidence functions were used to estimate relapse incidence (RI) and non-relapse mortality (NRM) in a competing risk setting. Death and relapse were considered as competing events for acute and chronic GVHD. Univariate analyses were done using the Gray's test for cumulative incidence functions and the log rank test for OS and PFS. A Cox proportional hazards model was used for multivariate regression, results were expressed as hazard ratio (HR) with a 95% confidence interval (CI). All tests were two-sided, type-1 error was fixed at 5%. Results: One hundred patients met eligibility criteria, 18-87 years old, 69 of which were Black, 27 Hispanic, and 2 of Asian descent. Sixty-seven patients had acute ATLL and 22 lymphomatous. In total, 22 patients underwent SCT with 17 allo-SCT and 5 autologous SCT (ASCT) between 2005-2020 with a median follow-up of 62 months. Ten patients (45%) were transplanted in first complete remission (CR1), and 15 (68%) had KPS ≥90. Among patients undergoing allo-SCT, 41% had matched sibling donors (MSD), 18% matched unrelated (MUD), and 35% haploidentical. The 1-year and 3-years rates of overall survival from diagnosis of the cohort were 42% and 21%, respectively. Acute ATLL subtype was a strong predictor of worse outcome (Figure 1) with 1-year and 3-years OS of 32% vs 71% (p=0.004) and 11% vs 46% (p=0.002), respectively, compared to lymphomatous disease. To account for immortal time bias, 37 non-transplanted patients with early mortality within 4 months of diagnosis that were not able to make it to transplant were excluded from the Kaplan-Meier survival analysis. Patients undergoing transplant had improved outcomes compared to non-transplanted patients (Figure 1, Table 1), with allo-SCT reaching statistical significance in multivariate analysis compared to the non-transplant group with OS HR of 0.3 (p=0.004) compared to 0.7 (p=0.6) in ASCT vs non-transplant. In transplanted patients, the 3-year RI and NRM were 51% and 37%, respectively, and 3-year PFS and OS were 31% and 39%, respectively. Four of five patients who received ASCT rapidly relapsed with 3 dying from disease progression and one lost to follow-up, with 1-year RI of 80% vs 30% in allo-SCT (p=0.03). In exploratory multivariate analysis, patients achieving CR1 and with good baseline performance scores (KPS >90) had significantly better outcomes compared to their counterparts regardless of transplant type, and surprisingly, race was a strong and significant predictor of outcomes affecting PFS and OS with Hispanic vs Black PFS and OS HRs of 6 (p=0.04) and 10 (p=0.04), respectively. Thirteen patients died within 2 years, eight from relapse/progression including 3 ASCT patients, and 4 from transplant-related toxicities. Conclusion: Our data suggest that allo-SCT, but not ASCT, is a valid option in select ATLL patients. It also appears that patients of Hispanic descent have worse outcome post-transplant but not overall, which could be explained by lack of compatible donors or barriers to early transplant. Although this is the largest NA-ATLL transplant cohort presented to date outside of Japan and Europe, further studies are necessary to fully explain these discrepancies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Allogeneic Stem Cell Transplant for Myelodysplastic Syndrome in the New Molecular Era of IPSS-M

Apart from various HSCT forms, its outcomes are closely related to the biology and molecular genetics of the original disease as well as its status prior to the procedure. However, early in the management the ability for general prognostication in terms of HSCT planning is crucial, as this is the only curative modality available for MDS patients. Molecular markers have well established interactions with disease modifying treatment (DMT) such as HMA and particularly HSCT. Therefore, an urgent unmet need of our new molecular era has been the translation of such data into empowered prognostications tools, historically relying on hematological and cytogenetics parameters. The quest for incorporating molecular information into MDS prognostication culminated in the recent development of the IPSS-M.1 A caveat of this score is that it really projects clinical outcomes based on a virtual assumption that the patients would not be treated. Indeed, only 30% of the cohort used in the original study received DMT, and only 9% underwent HSCT, thereby limiting its applicability in a specific transplant setting. Cognizant of the instrumental clinical utility of precisely allocating MDS patients to HSCT, a procedure possibly burdened by a high rate of complications, we explored IPSS-M and transplant interactions in a large, real-life cohort of MDS patients. With the joint efforts of an international collaborative, we accrued a total of 416 MDS patients undergone HSCT with comprehensive baseline molecular annotations and detailed clinical information on transplant-specific variables and outcomes. Overall, the median age at MDS diagnosis was 62 years (IQR 53-67) with a 1.6 M:F ratio. According to IPSS-R, patients clustered in Very Low (5%), Low (17%), Intermediate (16%), High (27%) and Very High (35%) risk groups. In 36% of cases, no therapy with DMT had been established prior to HSCT, whereas majority (85%) of treated cases received HMA as a bridge to transplant with an overall response rate of 25%. HSCT was performed after a median time of 6.6 months (95% CI 6.1-7.3) from MDS onset. Donor choice consisted of matched related (MRD) in 20%, matched unrelated (MUD) in 60%, haploidentical in 6%, and mismatched unrelated (MMUR) in 14% of our cohort. Majority of cases underwent reduced intensity conditioning regimens (74%). As a result, peripheral blood stem cells served as graft source in 84% of cases, whereas only 16% received bone marrow. With a median follow-up time of 51 months (95% CI; 44-58 months) after HSCT, the 5-year overall (OS) and Relapse-free survival (RFS) achieved 46% and 40%, respectively. Post-HSCT relapse/leukemic progression occurred in 29% of patients at a median of 7.7 months (3.4-22.8) from the procedure, whereas 28% and 45% experienced grade II-IV acute (aGvHD) and all-grade chronic graft-vs-host-disease (cGvHD), respectively. We then computed IPSS-M scores which resulted in a redistribution of risk categories as follows: Very Low (27%), Low (18%), Moderate Low (14%), Moderate High (15%), High (10%), and Very High (16%). OS at 5 years according to IPSS-M was 51%, 63%, 53%, 41%, 32%, and 26%, respectively (P<0.001; Fig.1A). Compared to IPSS-R, the incorporation of molecular information led to a significant re-stratification of patients (P<0.001; Fig.1B). Indeed, 57% of our cases carried IPSS-M molecular markers, thereby corroborating such observed differences in risk group allocation. In an attempt to assess the clinical utility of IPSS-M and its incremental benefit as opposed to IPSS-R in estimating OS/RFS outcomes in transplanted MDS, we computed Harrell's c-statistics. In terms of OS, IPSS-M resulted in a c-index of 0.583 vs 0.547 of the previous prognostication system, whereas in terms of RFS c-index was 0.584 vs 0.552, respectively. In conclusion, the addition of molecular information represents a crucial (although still modest) advantage in prognostication of MDS undergoing HSCT. Despite being a potential useful addition for the clinical management at diagnosis, it must be acknowledged that IPSS-M inherited all the limits of its prior version, being built in a largely HSCT-naive cohort. The lower performance indexes found in ours as compared to the original study highlight that in the HSCT setting additional risk factors inherent to the transplant procedure may still hold a prognostic significance beyond the consideration of disease-specific variables. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparison of Allogeneic Hematopoietic Cell Transplantation Outcomes from Younger Matched Unrelated Donor Versus Older Sibling Donor for Acute Myeloid Leukemia

Background: Aging population has resulted in an increase in the incidence of acute myeloid leukemia (AML). The median age of diagnosis for AML is 68 years. Allogeneic hematopoietic cell transplant (alloHCT) is a curative modality for patients with AML, however, disease relapse remains a major issue. Human leukocyte antigen (HLA)-matched sibling donors (MSD) are considered the preferred donor type in clinical practice. However, with increasing median age of patients, sibling donors for these patients are likely to be older as well, often with higher comorbidities. Prior registry studies demonstrated that older donor age is associated with inferior survival. A recent study in older MDS patients demonstrated reduced relapse risk with improved disease-free survival (DFS) with younger matched unrelated donors (MUD). However, the impact of donor age and type on alloHCT outcomes in AML patients remains unknown. Methods: This retrospective cohort study accessed data from the Center for International Blood and Marrow Transplant Research database (CIBMTR) in AML patients 50 years or older undergoing alloHCT from older (>50) MSDs or younger (<35) MUDs between 2011 and 2018. The study included common allograft types, conditioning regimens, and graft-versus-host-disease (GVHD) prophylaxis strategies. Other exclusion criteria were recipients of ex vivo T-cell depleted grafts, mismatched unrelated donor, cord blood or identical twin transplants. The primary outcome, compared between the 2 donor age groups, was relapse risk, and secondary outcomes included non-relapse mortality (NRM), DFS, and overall survival (OS). Cumulative incidence estimates were calculated for competing risks outcomes. To evaluate potential risk factors, multivariable cox regression was used, and relevant transplant-related covariates were considered. Interactions between the main effect (donor age group) and significant risk factors were tested. Fine and gray model was used for NRM and relapse. Results: Among 4684 eligible patients in the study cohort, 1736 underwent alloHCT with an older MSD (median age, 61 [range: 50-80]) whereas 2948 received transplant from a younger MUD (median age, 63 [range: 50-84]). In multivariable analysis, younger MUDs conferred a significantly decreased risk of relapse (HR 0.86; 95% CI, 0.77-0.96; p=.005) as compared to older MSDs (Table 1; Figure 1). The adjusted cumulative incidence of relapse at 5 years was significantly lower with younger MUDs (35%; 95% CI, 33-37%) versus older MSDs (41%; 95% CI, 38%-43%) (p=.003) (Table 2). NRM was reported in 2 subgroups of transplant years (2011-2015 and 2016-2018) as there was significant interaction between the main effect (MUD vs MSD) and alloHCT year (p=.003). Younger MUDs conferred an increased NRM (HR 1.24; 95% CI, 1.04-1.49; p=.016) compared to older MSDs in the earlier period of 2011-2015, whereas the NRM was lower with younger MUDs in the latter period of 2016-2018 (HR, 0.78, 95% CI, 0.64-0.96; p=.017) (Table1; Figure 1). While there was no difference in the adjusted cumulative incidence of NRM at 5 years in the latter period (17% vs 20%; p=.147), NRM was significantly higher in AML patients who underwent alloHCT between 2011 and 2015 from a younger MUD (28%; 95% CI, 25-30%) compared to older MSDs (24%; 95% CI, 20%-27%; p=.045) (Table2). There was no difference in OS or DFS rates of alloHCT with younger MUDs vs older MSDs (OS: HR 1.02; 95% CI, 0.94-1.12; p=.607; DFS: HR 0.92; 95% CI, 0.85-1.01; p=.073) (Table 1; Figure 1). While the adjusted 5-year OS probability was 47% in each of the 2 cohorts (p=0.95), the adjusted 5-year DFS probability was 44% with younger MUDs (95% CI, 42%-46%) as compared to 41% with older MSDs (95% CI, 38%-43%; p=.04) (Table2). Conclusions: This large study from a prospectively collected registry data found significant relapse reduction in AML patients who underwent alloHCT with younger MUDs as compared to older MSDs and highlights that a younger MUD donor type exerts a stronger GVL effect and should be preferred when available. The higher NRM associated with younger MUDs has decreased in recent years, likely due to enhanced GVHD prophylaxis, infection preemption and preventative strategies, and supportive cares measures translating into improved leukemia-free survival. The results aid in donor selection and younger MUDs should be preferred in AML patients at a higher risk for post-alloHCT relapse. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Younger Matched Unrelated Donors Confer a Decreased Relapse Risk As Compared to Older Sibling Donors for Adult B-Cell ALL Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

Background: The incidence of acute lymphoblastic leukemia (ALL) has increased due to aging population and the median age at diagnosis is 56 years among adults. Allogeneic hematopoietic cell transplant (alloHCT) offers cure for ALL patients, however, disease relapse remains a major issue. Human leukocyte antigen (HLA)-matched sibling donors (MSD) are considered the ideal donor type, mainly due to lower incidence and severity of graft-versus-host-disease (GVHD) and improved disease-free survival (DFS) in ALL. However, siblings are also likely to be older, often with higher comorbidities, and adult ALL patients typically undergo reduced-intensity conditioning and need novel strategies to reduce the post-alloHCT relapse risk. While recent data have suggested relapse reduction and survival benefit with younger matched unrelated donors (MUD) in AML and MDS, the impact of donor age on alloHCT outcomes in adult ALL patients remain unknown. Methods: This retrospective cohort study from the Center for International Blood and Marrow Transplant Research database (CIBMTR) data in B-cell ALL patients 50 years or older, undergoing alloHCT from older (>50) MSDs or younger (<35) MUDs between 2011 and 2018, included common allograft types (PB vs BM), conditioning regimens (RIC/NMA vs MAC), and graft-versus-host-disease (GVHD) prophylaxis strategies (FK-based vs CSA-based vs. others). Other exclusion criteria were recipients of ex vivo T-cell depleted grafts, recipients of mismatched unrelated donors, cord blood or identical twin transplants. The primary outcome, compared between the 2 donor age groups, was relapse risk whereas secondary outcomes included non-relapse mortality (NRM), DFS, and overall survival (OS). Cumulative incidence estimates were calculated for competing risks outcomes, including NRM and relapse. The Kaplan-Meier method was used to estimate the probabilities for survival. To evaluate potential risk factors, multivariable cox regression was used, and relevant transplant-related covariates were considered. Interactions between the main effect (donor age group) and significant risk factors were tested. Fine and Gray model was used for NRM and relapse. Given the multicenter nature of the database, center effect was tested for OS by fitting a gamma frailty model. Results: Among 925 eligible patients in the study cohort, 386 underwent alloHCT with an older MSD (median age, 59 [range: 50-75]) whereas 539 received transplant from a younger MUD (median age, 60 [range: 50-77]). In multivariable analysis, younger MUDs conferred a significantly decreased risk of relapse (HR 0.68; 95% CI, 0.53-0.87; p=.002) versus older MSDs (Table 1; Figure 1). The adjusted cumulative incidence of relapse at 5 years was significantly lower with younger MUDs compared to older MSDs (26% vs 37%; p=.001) (Table 2). Younger MUDs conferred an increased NRM compared to older MSDs (HR 1.38; 95% CI, 1.05-1.82; p=.02) (Table1; Figure 1). The adjusted cumulative incidence of NRM at 5 years was also significantly higher in B-ALL patients who underwent alloHCT from younger MUDs compared to older MSDs (31% vs 22%; p=.006) (Table2). There were no differences in OS or DFS rates of alloHCT with younger MUDs vs older MSDs (OS: HR 1.09; 95% CI, 0.90-1.32; p=.37; DFS: HR 0.95; 95% CI, 0.79-1.14; p=.57) (Table 1; Figure 1). The adjusted 5-year OS probability was 48% in younger MUDs (95% CI, 43%-52%) and 51% among older MSDs (95% CI, 45%-56%; p=0.37). The adjusted 5-year DFS probability was 44% with younger MUDs (95% CI, 40%-49%) compared to 42% with older MSDs (95% CI, 37%-47%; p=.59) (Table2). Conclusions: This is the largest study to date performed in a mature, prospectively collected registry cohort that aids in donor selection and found significant relapse reduction in adult B-ALL patients who underwent alloHCT with younger MUDs as compared to older MSDs. The results highlight that younger MUD donor type exerts a stronger GVL effect and should be preferred in patients at a higher risk for post-alloHCT relapse. The higher NRM associated with younger MUDs will need enhanced GVHD prophylaxis, infection preemption and preventative strategies, and supportive cares measures to consolidate the leukemia-free survival. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impact of Anti-T-lymphocyte globulin dosing on GVHD and Immune reconstitution in matched unrelated myeloablative peripheral blood stem cell transplantation

Data on the influence of different Anti-lymphocyte globulin (ATLG) doses on graft versus host disease (GVHD) incidence and immune reconstitution in matched unrelated (MUD) allogeneic Stem cell transplantation (allo-SCT) is limited. This retrospective study conducted at the University Medical-Center Hamburg compares GVHD and Immune reconstitution after myeloablative MUD (HLA 10/10) PBSC allogeneic stem cell transplant between 30 mg/Kg (n = 73) and 60 mg/Kg (n = 216) ATLG. Detailed phenotypes of T, B natural killer (NK), natural killer T (NKT) cells were analyzed by multicolor flow at day 30, 100, and 180 posttransplant. Neutrophil and platelet engraftments were significantly delayed in the 60 mg/kg group with a higher Cumulative incidence of Infections (67% vs 75% p = 0.049) and EBV (21% vs 41% p = 0.049) reactivation at day 100 in this group. In the 30 mg/kg group, we observed a faster reconstitution of naïve-B cells (p < 0.0001) and γδ T cells (p = 0.045) at day+30 and a faster naïve helper T-cell (p = 0.046), NK-cells (p = 0.035), and naïve B-cell reconstitution (p = 0.009) at day+180. There were no significant differences in aGVHD, cGVHD, NRM, RI, PFS, and OS between the groups. The choice of ATLG dose has significant impact on IR but not on GVHD after MUD-allo-SCT. Higher doses are associated with delayed engraftment and increased infections.

Incidence of chronic graft versus host disease using post-transplant cyclophosphamide in HLA-matched versus haploidentical donors.

e19044 Background: Allogeneic hematopoietic cell transplant (allo-HCT) is the only potential cure for many hematologic cancers. Graft-versus-host disease (GVHD) is a significant cause of mortality after allo-HCT. Post-transplant cyclophosphamide (PTCy) in haploidentical HCT (haplo-HCT) has yielded survival outcomes similar to those seen in HLA-matched allo-HCT. Single center studies have demonstrated lower rates of chronic GVHD with the use of PTCy in HLA-matched allo-HCT. In this single center study, we analyzed the outcomes of HLA-matched and haplo-HCT in patients (pts) who received PTCy for GVHD ppx. Methods: Pts who received allo-HCT from matched related (MRD), matched unrelated (MUD), and haploidentical donors (Haplo) from Jan 2016 to July 2021 were identified. Pts who did not receive PTCy were excluded. Pts were divided into two groups – MRD/MUD and Haplo. Primary endpoint was cumulative incidence of chronic GVHD. Secondary endpoints were cumulative incidence of relapse, non-relapse mortality (NRM), and overall survival (OS) at 2-years. Comparisons were made based on log-rank test and a model for subhazard function of a failure event of primary interest with p &lt; 0.05 used as cut-off point for statistical significance. Results: 62 pts (45 MRD/MUD,17 Haplo) were included. Baseline characteristics were similar. Median follow-up was 342 days post-transplant. Most had a diagnosis of AML (50%), high/very high DRI (48%), and received RIC (55%). Cumulative incidence of chronic GVHD was 11% overall (95% CI 5.8-21.3%); 6% for MRD/MUD and 27% for Haplo (p = 0.045). Cumulative incidence of relapse was 28% overall (95% CI 18-42%); 34% for MRD/MUD and 13% for Haplo (p = 0.09). Two-year OS was 55% overall (95% CI 39.1- 68.7%); 53% for MRD/MUD and 61% for Haplo (p = 0.043). There was no significant difference in incidence of grade 2-4 acute GVHD or NRM between groups. Conclusions: PTCy resulted in a significantly lower incidence of chronic GVHD in MRD/MUD group compared to Haplo group. Although cumulative incidence of relapse was not statistically different between groups, OS was worse in the MRD/MUD allo-HCT group after PTCy and most deaths were due to relapse.[Table: see text]

Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors

Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear. To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs. This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020. Allo-HCT from an older MSD (donor age ≥50 years) or a younger MUD (donor age ≤35 years). The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival. Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P = .02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P = .07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P < .001), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96; P = .02), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65; P < .001), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92; P = .005), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98; P = .04). This cohort study found higher disease-free survival and lower relapse for allo-HCT in myelodysplastic syndrome using younger MUDs compared with older MSDs. The risk of nonrelapse mortality and GVHD was lower with older MSDs. These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.