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Background: T cell-replete haploidentical stem cell transplantation (haplo-SCT) is a valid therapeutic option for adult patients with high-risk acute myeloid leukemia (AML) lacking an HLA-matched sibling or unrelated donor.Method: We retrospectively analyzed the outcomes of 912 AML patients ≥45 years of age who had undergone haplo-SCT with either myeloablative conditioning (MAC; n = 373) or reduced intensity conditioning (RIC; n = 539) regimens.Results: The median follow-up was 31.1 and 25.7 months for MAC and RIC, respectively. The incidence of relapse and nonrelapse mortality (NRM) were 25.1% versus 28.7% and 31.0% versus 30.3% for MAC and RIC, respectively; 2-year leukemia-free survival (LFS) was 43.9% for MAC versus 41.0% for RIC. In multivariate analysis, the use of MAC versus RIC was not associated with a difference in the outcomes. Results were confirmed in the propensity score-weighted analysis. Disease status and performance status at transplantation were associated with outcomes. Notably, the use of posttransplantation cyclophosphamide was associated with reduced acute graft-versus-host disease (aGVHD) stage III-IV, and NRM and increased overall survival, LFS, and GVHD-free, relapse-free survival. The use of mobilized peripheral blood stem cells was associated with an increased risk of stage II-IV aGVHD.Conclusion: No differences were found between MAC and RIC regimens for haplo-SCT in adults with AML who were ≥45 years of age. The type of GVHD prophylaxis, disease status, and performance status were the major predictors of transplantation outcome. These results may serve as the background for randomized study comparing RIC versus MAC for haplo-SCT in adults with AML. [ABSTRACT FROM AUTHOR]

Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018. The recent decline in transplants corresponds to increased CAR-T treatments (1117 cases in 2021). Median age for auto-HSCT rose from 42 (1990-1994) to 58 years (2015-2021), with peripheral blood becoming the primary stem cell source post-1994. Allo-HSCT median age increased from 36 (1990-1994) to 54 (2015-2021) years, with mobilized blood as the primary source post-1998 and reduced intensity conditioning post-2000. Unrelated and mismatched allo-HSCT accounted for 50% and 19% of allo-HSCT in 2015-2021. Three-year overall survival (OS) after auto-HSCT improved from 56% (1990-1994) to 70% (2015-2021), p < 0.001, with a decrease in relapse incidence (RI) from 49% to 38%, while non-relapse mortality (NRM) remained unchanged (4%). After allo-HSCT, 3-year-OS increased from 33% (1990-1999) to 46% (2015-2021) (p < 0.001); 3-year RI remained at 39% and 1-year-NRM decreased to 19% (p < 0.001). Our data reflect advancements over 32 years and >40,000 transplants, providing insights for evaluating emerging DLBCL therapies., (© 2024. The Author(s).)

In the context of T-cell replete haploidentical stem cell transplantation (Haplo-SCT) using post-transplantation cyclophosphamide (PT-Cy), it is still unknown whether peripheral blood (PB) or bone marrow (BM) is the best graft source. While PB is associated with a higher incidence of graft-versus-host disease (GVHD), it may induce a stronger graft-versus-leukemia effect compared to BM, notably in acute myeloid leukemia (AML). From the EBMT registry database, we compared T-cell replete PB (n = 595) versus BM (n = 209) grafts in a large cohort of 804 patients over the age of 60 years who underwent Haplo-SCT with PT-Cy for an AML in first or second complete remission. The risk of acute GVHD was significantly higher in the PB group (Grade II-IV: HR = 1.67, 95% CI [1.10-2.54], p = 0.01; Grade III-IV: HR = 2.29, 95% CI [1.16-4.54], p = 0.02). No significant difference was observed in chronic GVHD or non-relapse mortality. In the PB group, the risk of relapse was significantly lower in the PB group (HR = 0.65, 95% CI [0.45-0.94], p = 0.02) and leukemia-free survival was significantly better (HR = 0.76, 95% CI [0.59-0.99], p = 0.04), with a trend toward better overall survival (HR = 0.78, 95% CI [0.60-1.01], p = 0.06). We conclude that in the specific context of Haplo-SCT with PT-Cy, PB grafts represent a valid option to decrease the risk of relapse and improve outcome of older AML patients who usually do not benefit from conditioning intensification., (© 2024 Wiley Periodicals LLC.)

Previous observations have reported controversial conclusions regarding cell dose and survival endpoints after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a retrospective analysis on 414 adult patients (median age 54 years, range, 18-74 years) with acute myeloid leukemia (AML) in first and second complete remission. They received a T-cell replete allogeneic HSCT from haploidentical donors, using peripheral blood stem cells, between 2006-2018. Median number of infused CD34+ was 6.58 × 10 6 /kg (range, 2.2-31.2 × 10 6 /kg). Graft-vs-host disease (GVHD) prophylaxis was post-transplant cyclophosphamide in 293 patients and anti-lymphocyte serum in 121 patients. Conditioning was myeloablative in 179 patients and reduced-intensity in 235 patients. After a median follow-up of 23.3 months (range, 12.1-41.8 months), 2-year overall survival (OS) was 64.5% (95% CI 59.3%-69.7%) with leukemia-free survival (LFS) of 57.3% (95% CI 51.8%-62.7%) and non-relapse mortality (NRM) of 23.3% (95% CI 19%-27.7%). Grades III-IV acute GVHD day+100 incidence was 14.6% while extensive chronic GVHD was 14.4% at 2-years. Thirteen (3.2%) patients experienced graft failure. We found the optimal CD34+/kg threshold defining high (n = 334) vs low cell dose (n = 80) at 4.96 × 10 6 . Recipients of >4.96 × 10 6 /kg CD34+ cells experienced less NRM (Hazard ratio [HR] 0.48; 95% CI 0.30-0.76) and prolonged LFS (HR 0.63; 95% CI 0.43-0.91) and OS (HR 0.60; 95% CI 0.40-0.88) compared to those in the lower cell dose cohort. Larger cohort studies are needed to confirm these findings., (© 2020 Wiley Periodicals, Inc.)

Acute graft-vs.-host disease (aGvHD) is one of the most frequent causes of transplant-related mortality (TRM) after allogeneic hematopoietic cell transplantation (alloHCT). Its treatment is complex and costly. The aim of this study was to retrospectively analyze the impact of country-specific socioeconomic factors on outcome of patients who experience severe aGvHD. Adults with hematological malignancies receiving alloHCT from either HLA-matched siblings ( n = 1,328) or unrelated donors ( n = 2,824) developing grade 3 or 4 aGvHD were included. In univariate analysis, the probability of TRM at 2 years was increased for countries with lower current Health Care Expenditure (HCE, p = 0.04), lower HCE as % of Gross Domestic Product per capita ( p = 0.003) and lower values of the Human Development Index ( p = 0.02). In a multivariate model, the risk of TRM was most strongly predicted by current HCE (HR = 0.76, p = 0.006). HCE >median was also associated with reduced risk of the overall mortality (HR 0.73, p = 0.0006) and reduced risk of treatment failure (either relapse or TRM; HR 0.77, p = 0.004). We conclude that country-specific socioeconomic factors, in particular current HCE, are strongly associated with survival of patients who experience severe aGvHD., (Copyright © 2020 Frankiewicz, Peczynski, Giebel, Harrington, Socié, Niederwieser, Scheid, Bornhäuser, Kröger, Elmaagacli, Afanasyev, Dreger, Rössig, Blaise, Kratz, Yakoub-Agha, Kremens, Niemeyer, Wulf, Blau, Penack, Greinix and Basak.)

Allogeneic stem cell transplantation (SCT) is potentially curative therapy in acute myeloid leukemia (AML). Marked improvement has been achieved with SCT from matched unrelated donors (MUDs) in recent years. However, there are limited data comparing the long-term outcomes (beyond 10 years) after SCT from sibling donors and MUDs in older patients with AML. We analyzed these outcomes in a large cohort of patients with AML (n = 1134), age ≥50 years, who were alive and leukemia-free 2 years after SCT from matched siblings (n = 848) or MUDs (n = 286), with a median follow-up of 8.9 years. The median age was 56 and 58 years after SCT from siblings and MUDs, respectively (P = .005). In the sibling group, 77%, 12%, and 11% were in first complete remission (CR1), second complete remission (CR2), and active leukemia at SCT compared with 50%, 25%, and 25% in the MUD group, respectively (P < .001). Sixty-one percent of siblings and 62% of MUDs had reduced-intensity conditioning (P = .78). The 10-year leukemia-free survival (LFS) of patients surviving leukemia-free 2 years after SCT was 72% and 62%, respectively (P = .30). Multivariate analysis identified active leukemia at SCT (hazard ratio [HR], 1.86; P = .0001) or CR2 (HR, 1.51; P = .02) compared with CR1, female recipients (HR, 0.71; P = .006), adverse cytogenetics (HR, 2.52; P = .01), and prior graft-versus-host disease (HR, 1.31; P = .04) as independent factors predicting LFS. Donor and conditioning type were not significant. The cumulative incidence was 15% and 17% (P = .97) for late relapse mortality and 13% and 21% for late nonrelapse mortality, respectively (P = .15). In conclusion, long-term LFS is similar, and patients who are leukemia-free 2 years after SCT can expect favorable outcomes with both donor types., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Although high-dose therapy and autologous stem cell transplant combined with novel agents continues to be the hallmark of first-line treatment in newly diagnosed transplant-eligible multiple myeloma patients, the impact of tandem autologous or autologous/reduced-intensity allogeneic transplant for patients with extramedullary disease (EMD) and high-risk cytogenetics is not yet defined. Here, we analyzed clinical and cytogenetic data from 488 adult myeloma patients with EMD undergoing single autologous (n = 373), tandem autologous (n = 84), or autologous-allogeneic transplant (n = 31) between 2003 and 2015. At least 1 high-risk abnormality was present in 41% (n = 202), with del(17p) (40%) and t(4;14) (45%) the most frequent. More than 1 high-risk abnormality was found in 54%. High-risk cytogenetics showed worse 4-year overall survival (OS) and progression-free survival (PFS) of 54% and 29%, respectively, versus 78% and 49% for standard-risk cytogenetics (P < .001). Co-segregation of high-risk abnormalities did not seem to affect outcome. Regarding transplant regimen, OS and PFS were 70% and 43% for single autologous versus 83% and 52% for tandem autologous and 88% and 58% for autologous-allogeneic (P = .06 and P = .30). In multivariate analysis high-risk cytogenetics were associated with worse survival (hazard ratio [HR], 2.00; P = .003), whereas tandem autologous significantly improved outcome versus single autologous transplant (HRs, .46 and .64; P = .02 and P = .03). Autologous-allogeneic transplant did not significantly differ in outcome but appeared to improve survival, but results were limited because of small population (HR, .31). In conclusion, high-risk cytogenetics is frequently observed in newly diagnosed myeloma with EMD and significantly worsens outcome after single autologous, whereas a tandem autologous transplant strategy may overcome onset poor prognosis., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Therapy-related acute myeloid leukemia (t-AML) arises as a late complication following antecedent solid tumors or hematologic diseases and their associated treatments. There are limited data regarding risk factors and outcomes following allogeneic hematopoietic cell transplantation (HCT) for t-AML following a prior solid tumor, and furthermore, the impact of myeloablative (MAC) vs reduced-intensity conditioning (RIC) on survival is unknown. The acute leukemia working party (ALWP) of the European society for blood and bone marrow transplantation (EBMT) performed a large registry study that included 535 patients with t-AML and prior solid tumor who underwent first MAC or RIC allogeneic HCT from 2000-2016. The primary endpoints of the study were OS and LFS. Patients receiving RIC regimens had an increase in relapse incidence (hazard ratio [HR], 1.52; 95% confidence interval [CI] 1.02-2.26; P = 0.04), lower LFS (HR, 1.52; 95% CI 1.12-2.05, P = 0.007), and OS (HR, 1.51; CI 1.09-2.09; P = 0.012). There were no differences in NRM and GRFS. Importantly, LFS and OS were superior in patients receiving ablative regimens due to a decrease in relapse. As NRM continues to decline in the current era, it is conceivable that outcomes of HCT for t-AML with prior solid tumor may be improved by careful patient selection for myeloablative regimens., (© 2018 Wiley Periodicals, Inc.)

This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34 + cell dose was 4.8 × 10 6 /kg (range, 1.7 to 22.9; n = 43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28days was 82% (range, 70% to 93%), at a median of 21days (range, 19 to 23). At 2years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1- and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1- and 2- year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19% (95% CI 7% to 31%). The 2-year nonrelapse mortality was 38% (95% CI 24% to 51%). This retrospective study of MF allo-SCT using family mismatched donors demonstrated feasibility of the approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression-free survival rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality need to be used, ideally in a multicenter prospective fashion., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

More than 60% of patients with non-Hodgkin lymphoma (NHL) are age >60 years at presentation. The purpose of this study was to compare the potential risks and benefits of allogeneic hematopoietic cell transplantation (alloHCT) in elderly patients with NHL with younger patients in a large sample, also taking into account comorbidity information. All patients age ≥18 years who had undergone alloHCT from a matched sibling or unrelated donor for NHL between 2003 and 2013 and were registered with the European Society for Blood and Marrow Transplantation were eligible for the study. The primary study endpoint was 1-year nonrelapse mortality (NRM). A total of 3919 patients were eligible and were categorized by age: young (Y), 18 to 50 y (n = 1772); middle age (MA), 51 to 65 y (n = 1967); or old (O), 66 to 77 y (n = 180). Follicular lymphoma was present in 37% of the patients; diffuse large B cell lymphoma, in 30%; mantle cell lymphoma, in 21%, and peripheral T cell lymphoma, in 11%. At the time of alloHCT, 85% of the patients were chemosensitive and 15% were chemorefractory. With a median follow-up of 4.5 years in survivors, NRM at 1 year was 13% for the Y group. 20% for the MA group, and 33% for the O group (P <.001), whereas relapse incidence and overall survival (OS) at 3 years in the 3 groups were 30%, 31%, and 28% (P = .355) and 60%, 54%, and 38% (P <.001), respectively. Multivariable adjustment for confounders, including sex, NHL subset, time from diagnosis, chemosensitivity, donor, and conditioning, confirmed older age as a significant predictor for NRM and OS, but not for relapse risk. Although comorbidity was a significant predictor of NRM in a subset analysis restricted to the 979 patients with comorbidity information available, age retained its significant impact on NRM. In conclusion, our data show that alloHCT in patients age >65 y provides similar NHL control as seen in younger patients but is associated with a higher NRM that is not fully explained by comorbidity. Thus, although alloHCT is feasible and effective in very old patients, the increased NRM risk must be taken into account when assessing the indication for alloHCT for NHL in this age group., (Copyright © 2018. Published by Elsevier Inc.)

Background: Anti-thymocyte globulin (ATG) is widely used to prevent graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (alloPBSCT). The goal of this study was to retrospectively assess the effect of ATG on outcomes in the setting of Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL)., Methods: In the analysis, 1170 adult patients undergoing alloPBSCT from human leucocyte antigen-matched sibling or unrelated donors in the first complete remission between 2007 and 2016 were included. ATG was used in 429/575 (75%) and 121/595 (20%) patients transplanted from unrelated or sibling donors, respectively., Results: The incidence of chronic GVHD was 35% for patients treated with ATG compared with 52% in those not receiving ATG (p < 0.001), while the rate of extensive chronic GVHD was 16% and 36%, respectively (p < 0.001). The probability of survival free from GVHD and relapse (GRFS) was 42% and 32%, respectively (p = 0.002). In a multivariate model, the use of ATG was associated with reduced risk of overall chronic GVHD (hazard ratio [HR] = 0.52, p < 0.001) and extensive chronic GVHD (HR = 0.46, p < 0.001). It was also associated with better GRFS (HR = 0.77, p = 0.007), despite increased risk of relapse (HR = 1.41, p = 0.02). No significant effect was found with regard to the risk of non-relapse mortality and overall mortality., Conclusions: The use of ATG for patients with Ph+ ALL undergoing alloPBSCT is associated with reduced risk of chronic GVHD without impact on survival and therefore, could be considered. However, increased risk of relapse suggests the need for strict monitoring of minimal residual diseases and appropriate interventions after transplantation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Busulfan/fludarabine (BuFlu) is a widely used conditioning regimen for patients with myeloid malignancies. The sequential FLAMSA (fludarabine + Ara-C + amsacrine chemotherapy) protocol followed by either cyclophosphamide and total body irradiation (FLAMSA-TBI) or cyclophosphamide and busulfan (FLAMSA-Bu) has shown remarkable activity in high-risk acute myelogenous leukemia (AML) patients. Here we compare the outcomes of AML patients transplanted in first complete remission (CR1) or second complete remission (CR2) after conditioning with BuFlu or FLAMSA. Eligible patients had their first allogeneic stem cell transplantation for AML in CR1 or CR2 between January 2005 and June 2016. Donors were matched related or unrelated with up to 1 mismatch. Conditioning consisted of either BuFlu or FLAMSA. Propensity score matching was applied and comparisons were performed using weighted Cox regression. BuFlu conditioning was used in 1197 patients, whereas FLAMSA-TBI and FLAMSA-Bu were used in 258 and 141 patients, respectively. Median follow-up of survivors was 24.72 months. In univariate analysis, relapse incidence (RI) was 30.3%, 21.9%, and 23.1% in the BuFlu, FLAMSA-TBI, and FLAMSA-Bu groups, respectively (P < .01), and nonrelapse mortality at 2 years was 16.1%, 16.4%, and 26.7%, respectively (P < .01). Leukemia-free survival (LFS) at 2 years was 53.6%, 61.6%, and 50.1%, respectively (P = .03). Weighted Cox regression revealed that FLAMSA-TBI compared with BuFlu was associated with lower RI (hazard ratio [HR], .64; 95% confidence interval [CI], .42 to .98; P = .04) and a trend for better LFS (HR, .72; 95% CI, .49 to 1.06; P = .09). These results suggest that compared with BuFlu, conditioning with FLAMSA-TBI leads to reduced RI at 2 years in AML patients transplanted in CR1 or CR2., (Copyright © 2018. Published by Elsevier Inc.)

Secondary acute myeloid leukemia (sAML) has been associated with inferior outcomes compared with de novo AML. Little is known about patient risk factors and outcomes in sAML after allogeneic hematopoietic stem cell transplantation (HCT); thus, this large systemic analysis of the European Society for Blood and Bone Marrow Transplantation registry was performed. This study included 4997 patients with sAML who received HCT from 2000 to 2016. In univariate analysis the 2-year cumulative incidence of chronic graft-versus-host disease (GVHD), relapse, and nonrelapse mortality (NRM) were 33.5% (95% confidence interval [CI], 32% to 34.9%), 33.7% (95% CI, 32.3% to 35.1%), and 27.5% (95% CI, 26.1% to 28.7%), respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) at 2 years were 44.5% (95% CI, 43% to 46%), 38.8% (95% CI, 37.4% to 40.3%), and 27.2% (95% CI, 25.9% to 28.6%), respectively. In multivariate analysis, patients receiving myeloablative regimens had decreased relapse (hazard ratio, .859; 95% CI, .761 to .97; P = .01), higher NRM (hazard ratio, 1.175; 95% CI, 1.03 to 1.341; P = .02), and no differences in OS, LFS, and GRFS compared with patients receiving reduced-intensity conditioning regimens. Active disease, adverse cytogenetics, older age, Karnofsky performance status (≤80%), ex vivo T cell depletion, other malignant hematologic diseases, and patient cytomegalovirus seropositivity were associated with inferior OS and LFS. These variables should be considered in patients with sAML in need of HCT, and further study regarding the impact of conditioning regimens on relapse is needed., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Dose intensity of the conditioning regimen has significant impact on the outcomes after stem cell transplantation (SCT) for acute myeloid leukemia. Most studies have shown more relapse, less nonrelapse mortality (NRM), and similar overall survival after reduced-intensity and myeloablative conditioning. There are limited data on the dose equivalence and expected outcomes of treosulfan-based compared with busulfan-based conditioning. We compared SCT outcomes after fludarabine with either intravenous busulfan at a myeloablative dose (FB4, 12.8 mg/kg, n = 1265) or a reduced dose (FB2, 6.4 mg/kg, n = 1456) or treosulfan at 42 g/m 2 (FT14, n = 403) or 36 g/m 2 (FT12, n = 168). Median patient age was 48, 60, 57, and 60 years in the FB4, FB2, FT14, and FT12 groups, respectively (P < .0001). Two-year overall survival was 58%, 53%, 53%, and 51%, respectively (P = .25). Multivariate analysis identified advanced age, advanced disease status, and secondary leukemia to be associated with worse survival. Relapse rate was 30%, 35%, 34%, and 40%, respectively. Relapse was more common after FB2, advanced age and disease status, secondary leukemia, and sibling donors. NRM was 17%, 18%, 21%, and 16%, respectively. NRM was least common after FT12 and more common with advanced age and disease status and unrelated donors. Treosulfan-based regimens were associated with lower rates of graft-versus-host disease. There was no difference in any outcome among patients in first complete remission at transplantation. However, there was better survival with treosulfan-based conditioning in advanced leukemia. In conclusion, survival is determined mostly by disease biology and is similar after various regimens. Treosulfan-based conditioning is more similar to myeloablative than to reduced-intensity conditioning but can be administered safely in older patients, with lower rates of graft-versus-host disease and possibly better outcomes in patients with active leukemia., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

No standard exists for the treatment of myelodysplastic syndrome relapsing after allogeneic stem cell transplantation. We performed a retrospective registry analysis of outcomes and risk factors in 698 patients, treated with different strategies. The median overall survival from relapse was 4.7 months (95% confidence interval: 4.1-5.3) and the 2-year survival rate was 17.7% (95% confidence interval: 14.8-21.2%). Shorter remission after transplantation ( P <0.001), advanced disease ( P =0.001), older age ( P =0.007), unrelated donor ( P =0.008) and acute graft- versus -host disease before relapse ( P <0.001) adversely influenced survival. At 6 months from relapse, patients had received no cellular treatment, (i.e. palliative chemotherapy or best supportive care, n=375), donor lymphocyte infusion (n=213), or a second transplant (n=110). Treatment groups were analyzed separately because of imbalanced characteristics and difficulties in retrospectively evaluating the reason for individual treatments. Of the patients who did not receive any cellular therapy, 109 were alive at 6 months after relapse, achieving a median overall survival from this landmark of 8.9 months (95% confidence interval: 5.1-12.6). Their 2-year survival rate was 29.7%. Recipients of donor lymphocytes achieved a median survival from first infusion of 6.0 months (95% confidence interval: 3.7-8.3) with a 2-year survival rate of 27.6%. Longer remission after first transplantation ( P <0.001) and younger age ( P =0.009) predicted better outcome. Among recipients of a second transplant, the median survival from second transplantation was 4.2 months (95% confidence interval: 2.5-5.9), and their 2-year survival rate was 17.0%. Longer remission after first transplantation ( P <0.001), complete remission at second transplant ( P =0.008), no prior chronic graft- versus -host disease ( P <0.001) and change to a new donor ( P =0.04) predicted better outcome. The data enabled identification of patients benefiting from donor lymphocyte infusion and second transplantation, and may serve as a baseline for prospective trials., (Copyright© 2018 Ferrata Storti Foundation.)

Outcomes after umbilical cord blood transplantation (UCBT) for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are unknown. We analyzed outcomes of 68 patients with poor-risk CLL/SLL who underwent reduced-intensity (RIC) UCBT from 2004 to 2012. The median age was 57 years and median follow-up 36 months; 17 patients had del 17p/p53mutation, 19 patients had fludarabine-refractory disease, 11 relapsed after autologous stem cell transplantation, 8 had diagnosis of prolymphocytic leukemia, 4 had Richter syndrome, and 8 underwent transplantation with progressive or refractory disease. The most common RIC used was cyclophosphamide, fludarabine, and total body irradiation (TBI) in 82%; 15 patients received antithymocyte globulin. Most of the cord blood grafts were HLA mismatched and 76% received a double UCBT. Median total nucleated cells collected was 4.7 × 10(7)/kg. The cumulative incidences (CI) of neutrophil and platelet engraftment were 84% and 72% at 60 and 180 days respectively; day 100 graft-versus-host disease (GVHD) (grade II to IV) was 43% and 3-year chronic GVHD was 32%. The CI of relapse, nonrelapse mortality, overall survival, and progression-free survival (PFS) at 3 years were 16%, 39%, 54%, and 45%, respectively. Fludarabine-sensitive disease at transplantation and use of low-dose TBI regimens were associated with acceptable PFS. In conclusion, use of RIC-UCBT seems to be feasible in patients with poor-risk CLL/SLL and improved outcomes were observed in patients with fludarabine-sensitive disease who received low-dose TBI regimens., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

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.)

Extra-nodal NK/T lymphoma (ENKTL) is rare and more frequently encountered in East Asia. The role of high-dose therapy and autologous stem cell transplantation (HDT-ASCT) for ENKTL is unclear. Twenty-eight evaluable patients who had undergone HDT-ASCT in Europe from 2000-2009 were studied. The median age was 47 years and patients had received a median of two lines of prior therapy. Some 57% of patients were not in complete remission or beyond first complete remission at HDT-ASCT. The 1-year non-relapse mortality (NRM) was 11%; 2-year progression-free survival (PFS) and overall survival (OS) rates were 41% and 52%, respectively. Notably, the 2-year PFS and OS for those with stage III/IV disease were 33% and 40%, respectively, with no relapses beyond 1-year post-HDT-ASCT. This is the largest analysis of HDT-ASCT for patients with ENKTL reported from the Western hemisphere. Survival is comparable to East Asian cohorts and outcomes are encouraging for patients with advanced disease.

Background: There is currently limited experience on the feasibility and efficacy of autologous stem cell transplantation in elderly patients with diffuse large B-cell lymphoma., Design and Methods: We analyzed the outcome of 2612 patients with diffuse large B-cell lymphoma treated with autologous stem cell transplantation between 2000 and 2005 and reported to the European Blood and Marrow Transplantation registry. Four hundred and sixty-three patients (18%) were > or =60 years old at the time of the transplant (median, 63 years). When compared to 2149 patients <60 years old at the time of transplantation, the elderly patients had more frequently received at least two treatment lines (76% vs. 57%, p<0.001), were less commonly in first complete remission at the time of transplantation (23 % vs. 30 %, p=0.005) and received their transplants later after diagnosis (median time 14 months vs.7.5 months, p<0.001)., Results: Non-relapse mortality was higher in elderly patients at 100 days (4.4 % vs. 2.8 %), at 1 year (8.7% vs. 4.7%) and at 3 years (10.8% vs. 6.5%) (p=0.002). With a median follow-up of 12 months for the surviving patients for the elderly group and 15 months for the younger group, the risk of relapse was 38% and 32%, respectively (p=0.006).The progression-free survival was 51% and 62%, respectively, at 3 years (p<0.001). The overall survival rate was 60% vs. 70%, respectively, at 3 years (p<0.001)., Conclusions: Autologous stem cell transplantation is feasible in selected elderly patients with diffuse large B-cell lymphoma, although non-relapse mortality is somewhat higher than in younger patients. Both progression-free and overall survival rates are promising taking into account the generally poorer outcome of elderly patients with diffuse large B-cell lymphoma.

This retrospective study reported the outcome of 97 adult acute lymphoblastic leukemia patients who received a reduced-intensity conditioning allogeneic stem cell transplantation. With a median follow-up of 2.8 years, two year overall-survival, leukemia-free survival and non-relapse mortality were significantly better in patients transplanted in first complete remission (CR1, 52+/-9%; 42+/-10%; and 18+/-7% respectively) compared with those transplanted in more advanced phase (p=0.003, p=0.002 and p=0.01 respectively). In multivariate analysis, disease status (CR1 vs. advanced; p=0.001) and chronic graft-vs-host disease (p=0.01) were associated with an improved overall-survival, suggesting that reduced-intensity conditioning allogeneic stem cell transplantation is feasible in patients with high risk lymphoblastic leukemia in remission at transplantation.

Acute megakaryoblastic leukemia (M7 AML) is a highly aggressive disease. We evaluated outcomes in 57 children (11 with Down syndrome) and 69 adults with M7 AML after first complete remission (CR1) following autologous or HLA-identical allogeneic transplantation. Characteristics of the recipients of autologous transplants (38 children, 37 adults) were, respectively: median age, 1.7 and 46 years; non-total body irradiation (non-TBI) conditioning regimen, 97% and 70%; bone marrow as stem cell source, 74% and 43%. Characteristics of the recipients of allogeneic transplants (19 children, 32 adults) were, respectively: median age, 2.8 and 37 years; non-TBI regimen, 63% and 42%; bone marrow as stem cell source, 95% and 69%. Autologous transplantation benefited children more; the relapse rate was high in adults. Results for autologous transplantation were (children and adults, respectively): engraftment, 90% and 100%; 3-year treatment-related mortality (TRM) rate, 3% and 8%; relapse rate, 45% and 64%; leukemia-free survival (LFS) rate, 52% and 27%; overall survival (OS) rate, 61% and 30%. After allogeneic transplantation, TRM was fairly low in children and adults, and relapse rates were lower than after autologous transplantation. Results for allogeneic transplantation were, respectively: engraftment, 95% and 90%; TRM, 0% and 26%; relapse rate, 34% and 28%; LFS, 66% and 46%; OS, 82% and 43%). We conclude that M7 AML patients in CR1 (except children with Down syndrome, who already have better outcomes) can benefit from transplantation.