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Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM), but direct comparisons are lacking. Leveraging an international multicenter RRMM cohort, we compared the outcome of ide-cel ( n  = 162) versus cilta-cel ( n  = 42). Co-primary efficacy endpoints of the study were overall response rate (ORR) and progression-free survival (PFS). Co-primary safety endpoints were the incidence of cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS). Median turnaround time between apheresis and infusion was 47 days for ide-cel versus 68 days for cilta-cel ( p  < 0.001). Cilta-cel showed significantly higher ORR (93% vs. 79%; p  < 0.001), with complete response at Day 30 of 48% versus 26% ( p  < 0.001). The 10-month PFS and overall survival (OS) was 82% and 90% for cilta-cel versus 47% and 77% ide-cel ( p  < 0.001 and p  = 0.06), and improved outcome for cilta-cel was confirmed after multivariable adjustment. Incidence of CRS and ICANS appeared similar (81% and 19% for cilta-cel versus 85% and 19% for ide-cel), while 10% and 7% in the cilta-cel group versus 4% and 2% in the ide-cel group showed severe CRS and ICANS grade 3-4, with CRS occurring significantly earlier for ide-cel (median, 2 days vs. 4 days; p  < 0.001). Nonrelapse mortality was 5% for cilta-cel versus 3% for ide-cel ( p  = 0.51). Cilta-cel showed later peak of CAR-T expansion at Day 14 versus Day 7 for ide-cel, while cilta-cel expansion was associated with ICANS. Our study provides real-world evidence that cilta-cel was associated with superior outcomes and distinct cellular dynamics versus ide-cel in triple-class exposed RRMM., Competing Interests: Nico Gagelmann: Consulting or Advisory Role: Stemline Therapeutics, MorphoSys Travel, Accommodations, Expenses: Bristol Myers Squibb/Celgene, Janssen. Maximilian Merz: Honoraria: Janssen, BMS GmbH & Co KG, Amgen, AbbVie, Stemline Therapeutics, Takeda, Sanofi, Pfizer Consulting or Advisory Role: Janssen, BMS GmbH & Co KG, Pfizer, Sanofi Research Funding: Janssen, SpringWorks Therapeutics, Roche/Genentech Travel, Accommodations, Expenses: Janssen, Stemline Therapeutics, Pfizer. Aina Oliver‐Caldés: Travel, Accommodations, Expenses: Janssen. Friedrich Stölzel: Honoraria: Medac, Jazz Pharmaceuticals, Consulting or Advisory Role: Glycostem, Travel, Accommodations, Expenses: SERVIER. Anca‐Maria Albici: Honoraria: AbbVie, Travel, Accommodations, Expenses: SERVIER. Natalie Schub: Honoraria: Janssen Oncology, Consulting or Advisory Role: BMS, Travel, Accommodations, Expenses: Kite/Gilead. Soraya Kharboutli: Honoraria: Bristol Myers Squibb GmbH, Travel, Accommodations, Expenses: Janssen, Bristol Myers Squibb, Sobi, Novartis. Fabian Müller: Honoraria: AstraZeneca, Bristol Myers Squibb/Pfizer, Kite/Gilead, Consulting or Advisory Role: Bristol Myers Squibb/Pfizer, Janssen, Kite/Gilead, Kite/Gilead, Novartis, Miltenyi Biomedicine, Research Funding: Kite/Gilead, Travel, Accommodations, Expenses: SOBI, Janssen. Vladan Vucinic: Honoraria: Janssen, BMS GmbH & Co KG, Gilead Sciences, Amgen, Consulting or Advisory Role: Gilead Sciences, Janssen, BMS GmbH & Co KG, Amgen, Travel, Accommodations, Expenses: Sobi, Janssen, Gilead Sciences, Amgen. Uwe Platzbecker: Honoraria: Celgene/Jazz, AbbVie, Curis, Geron, Janssen, Consulting or Advisory Role: Celgene/Jazz, Novartis, BMS GmbH & Co KG, Research Funding: Amgen (Inst), Janssen (Inst), Novartis (Inst), BerGenBio (Inst), Celgene (Inst), Curis (Inst), Patents, Royalties, Other Intellectual Property: Part of a patent for a TFR‐2 antibody (Rauner et al. Nature Metabolics 2019), Travel, Accommodations, Expenses: Celgene. Francis Ayuk: Honoraria: Bristol Myers Squibb/Celgene, Kite/Gilead, Janssen, Miltenyi Biomedicine, Novartis, Takeda, Mallinckrodt/Therakos, medac pharma, Consulting or Advisory Role: Bristol Myers Squibb/Celgene Research Funding: Mallinckrodt/Therakos. Nicolaus Kröger: Honoraria: Novartis, Celgene (Inst), Sanofi, Jazz Pharmaceuticals (Inst), Kite/Gilead, RIEMSER (Inst), AOP Orphan Pharmaceuticals, BMS GmbH & Co KG, Neovii, Alexion Pharmaceuticals, Takeda, Pierre Fabre Consulting or Advisory Role: Neovii, Sanofi, Jazz Pharmaceuticals, Novartis, Celgene, RIEMSER, Gilead Sciences, Speakers' Bureau: AOP Orphan Pharmaceuticals, Research Funding: Neovii (Inst), Novartis (Inst), Celgene (Inst), Riemser (Inst), Travel, Accommodations, Expenses: Neovii, Novartis, Gilead Sciences, Jazz Pharmaceuticals, Sanofi, Celgene. Carlos Fernández de Larrea: Honoraria: Janssen, BeiGene, Bristol Myers Squibb/Celgene, Pfizer, Amgen, GlaxoSmithKline Consulting or Advisory Role: Janssen, Bristol Myers Squibb/Celgene, Amgen, Pfizer, Sanofi, BeiGene Research Funding: Janssen (Inst), Bristol Myers Squibb/Celgene (Inst), Amgen (Inst), GlaxoSmithKline (Inst) Travel, Accommodations, Expenses: Janssen, Amgen, GlaxoSmithKline, Bristol Myers Squibb/Celgene, BeiGene, Pfizer. No other potential conflicts of interest were reported., (© 2025 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)

Information on late complications in patients with acute leukemia who have undergone allogeneic hematopoietic cell transplantation (HCT) is limited. We performed a left-truncated analysis of long-term survival in patients with acute leukemia who were alive and disease-free 2 years after HCT. We included 2701 patients with acute lymphoblastic leukemia (ALL) and 9027 patients with acute myeloid leukemia (AML) who underwent HCT between 2005 and 2012. The 10-year overall survival (OS) rate was 81.3% for ALL and 76.2% for AML, with the main causes of late mortality being relapse (ALL-33.9%, AML-44.9%) and chronic graft-versus-host disease (ALL-29%, AML-18%). At 10 years, HCT-related mortality was 16.8% and 20.4%, respectively. Older age and unrelated donor transplantation were associated with a worse prognosis for both types of leukemia. In addition, transplantation in the second or third complete remission and peripheral blood HSC for ALL are associated with worse outcomes. Similarly, adverse cytogenetics, female donor to male patient combination, and reduced intensity conditioning in AML contribute to poor prognosis. We conclude that 2-year survival in remission after HCT for acute leukemia is encouraging, with OS of nearly 80% at 10 years. However, the long-term mortality risk of HCT survivors remains significantly higher than that of the age-matched general population. These findings underscore the importance of tailoring transplantation strategies to improve long-term outcomes in patients with acute leukemia undergoing HCT., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)

Background: The aim of this study was to compare two immunosuppressive strategies, based on the use of either rabbit antithymocyte globulin (ATG) or posttransplant cyclophosphamide (PTCY), as a prophylaxis of graft-versus-host disease (GVHD) for patients with acute lymphoblastic leukemia (ALL) in first complete remission who underwent hematopoietic cells transplantation from matched unrelated donors., Methods: Overall, 117 and 779 adult patients who received PTCY and ATG, respectively, between the years 2015 and 2020 were included in this retrospective study. The median patient age was 40 and 43 years in the PTCY and ATG groups, respectively, and 37% and 35% of patients, respectively, had Philadelphia chromosome-positive ALL., Results: In univariate analysis, the cumulative incidence of acute and chronic GVHD did not differ significantly between the study groups. The cumulative incidence of relapse at 2 years was reduced in the PTCY group (18% vs. 25%; p = .046) without a significant impact on nonrelapse mortality (11% vs. 16% in the ATG group; p = .29). The rates of leukemia-free survival (LFS) and overall survival were 71% versus 59%, respectively (p = .01), and 82% versus 74%, respectively (p = .08). In multivariate analysis, the receipt of ATG compared with PTCY was associated with a reduced risk of extensive chronic GVHD (hazard ratio, 0.54; 95% confidence interval, 0.3-0.98; p = .04) and an increased risk of low LFS (hazard ratio, 1.57; 95% confidence interval, 1.01-2.45; p = .045)., Conclusions: The receipt of ATG compared with PTCY, despite the reduced risk of extensive chronic GVHD, is associated with inferior LFS in adults with ALL who undergo hematopoietic cell transplantation from 10/10 human leukocyte antigen-matched unrelated donors. These findings warrant verification in prospective trials., (© 2023 American Cancer Society.)

Recent evidence revealed important interactions between clonal hematopoiesis (CH) and cellular therapies established for the treatment of hematologic malignancies. The impact of CH on safety, efficacy, and outcome of chimeric antigen receptor (CAR) T-cell therapy is currently under investigation. We analyzed 110 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (n = 105) or acute lymphoblastic leukemia (ALL) (n = 5), treated with Axicabtagene-Ciloleucel (39%), Tisagenlecleucel (51%), or Brexucabtagene autoleucel (10%). Using error-corrected targeted sequencing, a high CH prevalence of 56.4% (variant allele frequency [VAF] ≥1%) at the time of CAR T-cell infusion was detected. The most frequently mutated gene was PPM1D followed by DNMT3A , TET2 , ASXL1 , and TP53 . Variant allele frequencies were significantly lower in B and T cells compared with monocytes and granulocytes. CH did not increase the risk of CAR T-related toxicities. The incidences of cytokine release syndrome and immune effector-cell-associated neurotoxicity syndrome were similar between CH pos and CH neg patients, regardless of clone size, age, or CAR T product. Prolonged cytopenias were not associated with CH. Best overall response rates (ORRs) were numerically but not significantly higher in CH pos patients (ORR 76.7% versus 62.2%; P = 0.13). Furthermore, CH status did not predict progression-free survival or overall survival. Lastly, sequential analysis showed a modest VAF increase of 1.3% and acquisition of novel mutations within 100 days postinfusion. CH was frequent in large B-cell lymphoma/ALL patients receiving CAR T-cells but did not affect toxicity nor treatment response or outcome., Competing Interests: MH reports fees for advisory or consultancy services from Abbvie, Agios, BMS, Daiichi Sankyo, Eurocept, Glycostem, Janssen, Jazz Pharmaceuticals, Kura Oncology, Novartis, Pfizer, PinotBio, Roche, Takeda, and Tolremo. FD reports personal fees from Gilead, Incyte, Roche, Novartis, AbbVie, Astra Zeneca outside the submitted work. JFK reports personal fees from Gilead and Janssen outside the submitted work. GW reports honoraria from Gilead, Novartis, Clinigen, and Janssen outside the submitted work. OP has no conflicts of interest directly related to this work. OP has received honoraria or travel support from Gilead, Jazz, MSD, Novartis, Pfizer, and Therakos. He has received research support from Incyte and Priothera. He is member of advisory boards to Equillium Bio, Jazz, Gilead, Novartis, MSD, Omeros, Priothera, Sanofi, Shionogi, and SOBI. All the other authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) is the only cure for acute myeloid leukemia (AML) in second complete remission (CR2). Patients lacking a matched sibling donor (MSD) receive transplants from matched unrelated donors (MUDs), mismatched unrelated donors (MMUDs), haploidentical (haplo) donors, or cord blood., Methods: This is a retrospective, registry-based European Society for Blood and Marrow Transplantation study that investigates changes in patient- and transplant-related characteristics and posttransplant outcomes over time., Results: We identified 3955 adult patients (46.7% female; median age, 52 years [range, 18-78 years]) with AML in CR2 first transplanted between 2005 and 2019 from a MUD 10/10 (61.4%), MMUD 9/10 (21.9%), or haplo donor (16.7%) and followed for 3.7 years. A total of 725 patients were transplanted between 2005 and 2009, 1600 between 2010 and 2014, and 1630 between 2015 and 2019. Over the three time periods, there was a significant increase in patient age (from 48.7 to 53.5 years; p < .001), use of a haplo donor (from 4.6% to 26.4%; p < .001), and use of posttransplant cyclophosphamide (from 0.4% to 29%; p < .001). There was a significant decrease in total body irradiation and in vivo T-cell depletion. In multivariate analysis, transplants performed more recently had better outcomes. Leukemia-free survival (hazard ratio [HR], 0.79; p = .002) and overall survival (HR, 0.73; p < .001) increased over time. Similarly, nonrelapse mortality (HR, 0.64; p < .001) decreased over time. We also observed better graft-vs-host disease (GVHD) rates (acute GVHD II-IV: HR, 0.78; p = .03; GVHD-free, relapse-free survival: HR, 0.69; p < .001)., Conclusions: Even in the absence of an MSD, outcomes of allo-HCT in CR2 for AML have significantly improved over time, with most favorable outcomes achieved with a MUD., (© 2023 American Cancer Society.)

Hematopoietic cell transplantation (HCT) is a curative approach for myelofibrosis patients, but relapse is a major cause of treatment failure. We investigated the effect of donor lymphocyte infusion (DLI) in 37 patients with molecular (n = 17) or hematological relapse (n = 20) after HCT. Patients received median of 2 (range, 1-5) cumulative DLI (total of 91 infusions). Median starting dose was 1 × 10 6 cells/kg, escalated by half-log ≥6 weeks if no response nor graft-versus-host disease (GvHD) occurred. Median time to first DLI was 40 weeks for molecular relapse versus 145 weeks for hematological relapse. Overall molecular complete response (mCR) at any time was 73% (n = 27) and was significantly higher for initial molecular relapse (88%) versus hematological relapse (60%; P = 0.05). The 6-year overall survival was 77% versus 32% ( P = 0.03). Acute GvHD 2-4 occurred in 22% and half of the patients achieved mCR without any GvHD. All patients who relapsed from mCR achieved after first DLI could be salvaged with subsequent DLI, showing long-term survival. No second HCT was needed for molecular relapse versus 6 for hematological relapse. This comprehensive and largest study to date suggests molecular monitoring together with DLI as standard of care and a crucial approach to achieve excellent outcomes in relapsed myelofibrosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Availability of haploidentical donors has broadened utilization of allogeneic hematopoietic cell transplantation (allo-HCT). Peripheral blood stem cells (PBSC) are being used with increased frequency in haploidentical allo-HCT. We evaluated extent of HLA disparity (2-3/8 versus 4/8 HLA antigen mismatches) on post-allograft outcomes when using T-cell replete PBSC from haploidentical donors for acute myeloid leukemia in first complete remission. Primary objectives entailed assessing cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD (any grade). A total of 645 patients received a haploidentical allo-HCT from a donor with either 2-3 of 8 HLA antigen mismatches (n = 180) or with 4 of 8 HLA antigen mismatches (n = 465). Presence of 2-3 of 8 versus 4 of 8 HLA mismatches did not affect the incidence of acute GVHD (grade 2-4) and chronic GVHD (any grade). Overall survival (OS), leukemia-free survival (LFS) relapse incidence (RI), nonrelapse mortality and the composite endpoint of GVHD-free relapse-free survival were also similar among the groups. Pertaining to HLA-B leader matching effect, our analysis did not discern any difference in aforementioned post-allograft outcomes for this variable. However, in univariate analysis, absence of an antigen mismatch in HLA-DPB1 showed a trend for better OS. Notwithstanding inherent limitations associated with registry data, our results did not show an advantage of selecting a haploidentical donor with 2-3 of 8 HLA antigen mismatches over one with 4 of 8 HLA antigen mismatches when using PBSC as the cell source. Adverse cytogenetics remains a major adverse determinant of inferior OS and LFS and a higher RI. Using reduced-intensity conditioning yielded worse OS and LFS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Graft versus host disease (GVHD) prophylaxis with posttransplantation cyclophosphamide (PTCY) has been established to reduce severe GVHD, and thereby potentially reducing nonrelapse mortality (NRM) after allogeneic stem cell transplantation (alloSCT). We evaluated the predictive capacity of established NRM-risk scores in patients receiving PTCY-based GVHD prophylaxis, and subsequently developed and validated a novel PTCY-specific NRM-risk model. Adult patients (n = 1861) with AML or ALL in first complete remission who received alloSCT with PTCY-based GVHD prophylaxis were included. The PTCY-risk score was developed using multivariable Fine and Gray regression, selecting parameters from the hematopoietic cell transplantation-comorbidity index (HCT-CI) and European Group for Blood and Marrow Transplantation (EBMT) score with a subdistribution hazard ratio (SHR) of ≥1.2 for 2-year NRM in the training set (70% split), which was validated in the test set (30%). The performance of the EBMT score, HCT-CI, and integrated EBMT score was relatively poor for discriminating 2-year NRM (c-statistic 51.7%, 56.6%, and 59.2%, respectively). The PTCY-risk score included 10 variables which were collapsed in 3 risk groups estimating 2-year NRM of 11% ± 2%, 19% ± 2%, and 36% ± 3% (training set, c-statistic 64%), and 11% ± 2%, 18% ± 3%, and 31% ± 5% (test set, c-statistic 63%), which also translated into different overall survival. Collectively, we developed an NRM-risk score for acute leukemia patients receiving PTCY that better predicted 2-year NRM compared with existing models, which might be applicable to the specific toxicities of high-dose cyclophosphamide., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

In this registry-based study, we compared outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) in adult patients with acute lymphoblastic leukemia (ALL) transplanted in first complete remission (CR-1), following conditioning with total body irradiation (TBI) at a standard 12-Gray or at a lower 8-Gray total dose. Patients received fludarabine (flu) as the sole chemotherapy complementing TBI. Eight-Gray TBI/flu was used in 494 patients and 12-Gray TBI/flu in 145 patients. Eighty-eight (23.1%) and 36 (29%) of the patients had Ph-negative B-ALL, 222 (58.3%) and 53 (42.7%) had Ph-positive B-ALL, 71 (18.6%) and 35 (28.2%) T-ALL, respectively ( P = 0.008). Patients treated with 8-Gray were older than ones received 12-Gray (median 55.7 versus 40.3 years, P < 0.0001) and were more frequently administered in vivo T-cell depletion (71% versus 40%, P <0.0001). In a multivariate model adjusted for age, type of ALL, and other prognostic factors, leukemia-free survival (primary endpoint) as well as relapse, nonrelapse mortality, overall survival, and GVHD-free, relapse-free survival were not influenced by the TBI dose. These results were confirmed when we focused on patients <55 years of age (median 47 years). Patients with Ph-positive ALL or T-ALL had significantly better survival outcomes than ones with Ph-negative B-ALL, mainly due to significantly fewer relapses. We conclude that 8-Gray TBI is sufficient for adult patients with ALL transplanted in CR-1 with no additional benefit of augmenting the conditioning intensity to 12-Gray., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Background: Both mismatched unrelated donor (MMUD) and haploidentical (haplo) transplantation are valid options in patients with high-risk acute lymphoblastic leukemia (ALL) lacking a matched donor., Methods: The study compared the outcomes of adult patients with ALL in complete remission (CR) who underwent 9/10 MMUD versus haplo transplantation with posttransplant cyclophosphamide (PTCy) as graft-vs-host disease (GVHD) prophylaxis in 2010-2020., Results: The study included 781 patients (MMUD, 103; haplo, 678). The median age was 40 (19-73) and 38 (18-75) years, respectively (p = .51). The most frequent immunosuppression agents added to PTCy were mycophenolate mofetil (MMF)/cyclosporine A and MMF/tacrolimus. In vivo T-cell depletion (anti-thymocyte globulin) was administered to 21% and 8% of the transplants, respectively (p < .0001). Neutrophil (absolute neutrophil count >0.5 × 10 9 /L) recovery was achieved in 97.1% versus 96.7% versus (p = 1) in MMUD and haplo, respectively. Nonrelapse mortality and relapse incidence were not significantly different between MMUD and haplo, hazard ratio (HR) = 1.45 (95% confidence interval [CI], 0.81-2.62; p = .21) and HR = 0.81 (95% CI, 0.52-1.28, p = .38), respectively. HRs for leukemia-free survival, overall survival, and GVHD-free, relapse-free survival were respectively, HR = 1.05 (95% CI, 0.73-1.50, p = .8), HR = 1.17 (95% CI, 0.77-1.76, p = .46), and HR = 1.07 (95% CI, 0.78-1.46, p = .7) for haplo compared to MMUD. Acute (a)GVHD grade 2-4 was significantly higher with haplo, HR = 1.73 (95% CI, 1.08-2.76, p = .023), whereas aGVHD grade 3-4 and chronic GVHD did not differ significantly between the two transplant groups., Conclusion: Outcomes of MMUD and haplo transplants with PTCy-based GVHD prophylaxis for ALL patients in CR are similar, apart from a higher incidence of aGVHD with haplo transplants., (© 2022 American Cancer Society.)

There is no direct evidence to recommend specific conditioning intensities in myelofibrosis undergoing allogeneic hematopoietic cell transplantation, especially in the molecular era. We aimed to compare outcomes of reduced intensity (RIC) or myeloablative conditioning (MAC) transplantation in myelofibrosis with molecular information. The study included 645 genetically annotated patients (with at least driver mutation status available), of whom 414 received RIC and 231 patients received MAC. The median follow-up time from transplantation was 6.0 years for RIC and 9.4 years for MAC. The 6-year overall survival rates for RIC and MAC were 63% (95% confidence interval [CI], 58%-68%) and 59% (95% CI, 52%-66%; P = 0.34) and progression-free survival was 52% (95% CI, 47%-57%) and 52% (95% CI, 45%-59%; P = 0.64). The 2-year cumulative incidence of nonrelapse mortality was 26% (95% CI, 21%-31%) for RIC and 29% (95% CI, 23%-34%) for MAC ( P = 0.51). In terms of progression/relapse, the 2-year cumulative incidence was 10% (95% CI, 5%-19%) for RIC and 9% (95% CI, 4%-14%) for MAC ( P = 0.46). Higher intensity conditioning did not seem to improve outcomes for higher-risk disease, according to mutational, cytogenetic, and clinical profile. In contrast, patients with reduced performance status, matched unrelated donors, and ASXL1 mutations appeared to benefit from RIC in terms of overall survival., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Objective: Prior to hematopoietic stem cell transplantation (HSCT), and despite the high objective risks associated with HSCT, fear of progression (FoP) has only sparsely been studied in patients with acute leukemia until now. The aim of this study was the assessment of the prevalence of FoP, and any relevant correlates and typical concerns., Methods: We included 59 adult patients with acute leukemia who were tested prior to their first HSCT during an in-patient stay. Patients completed self-report measures assessing FoP (Fear of Progression Questionnaire-Short Form, FoP-Q-SF) and relevant correlates of FoP (eg, patients' physical state, depression, psychosocial distress, or social support)., Results: About one third of the patients (35.6%; n = 21) had high FoP. Higher FoP was associated with previous cancer diagnosis, as well as depression, anxiety, reduced physical functioning, lower mental health-related quality of life, and lower positive social support. The greatest fears reported by these patients reflected common fears of cancer patients (eg, fear about leaving their families behind), but also specific fears related to the current situation (eg, fear of severe medical treatments during the course of the illness)., Conclusions: This was the first study providing an extensive analysis of FoP in leukemia patients prior to the extreme situation of HSCT. FoP is frequent and of major clinical importance for these patients. Hence, we recommend that patients undergo routine screening for FoP, to identify highly distressed patients at an early stage, and to offer targeted support., (© 2020 John Wiley & Sons, Ltd.)

Background: In this prospective multicenter study, we investigated cancer-and-treatment-specific distress (CTXD) and its impact on symptoms of posttraumatic stress disorder (PTSD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT)., Methods: Patients were consulted before (T0, N = 239), 3 (T1, N = 150), and 12 months (T2, N = 102) after HSCT. Medical (eg, diagnosis and pretreatment) and demographic information, CTXD and PTSD (PCL-C) were assessed., Results: Random intercept models revealed that the sum score of CTXD was highest pre-HSCT (T0), decreased by T1 (γ = -.18, 95% CI [-.26/-.09]), and by T2 (γ = -.10, 95% CI [-.20/-.00]). Uncertainty, family strain, and health burden were rated most distressing during HSCT. Uncertainty and family strain decreased from T0 to T1 (γ = -.30, 95% CI [-.42/-.17]; γ = -.10, 95% CI [-.20/-.00]) and health burden from T1 to T2 (γ = -.21, 95% CI [-.36/.05]). Women were more likely to report uncertainty (γ = .38, 95% CI [.19/.58]), family strain (γ = .38, 95% CI [.19/.58]), and concerns regarding appearance and sexuality (γ = .31, 95% CI [.14/.47]) than men. Uncertainty (γ = .18, 95% CI [.12/.24]), appearance and sexuality (γ = .09, 95% CI [.01/.16]), and health burden (γ = .21, 95% CI [.14/.27]) emerged as predictors of PTSD symptomatology across the 3 assessment points., Conclusions: Our data provide first evidence regarding the course of 6 dimensions of CTXD during HSCT and their impact on PTSD symptomatology. Specifically, results emphasize the major burden of uncertainty pre-HSCT and the impact of uncertainty and concerns regarding appearance and sexuality on PTSD symptomatology., (Copyright © 2016 John Wiley & Sons, Ltd.)

Demethylating agent, 5-Azacytidine (5-Aza), has been shown to be active in treatment of myeloid malignancies. 5-Aza enhances anticancer immunity, by increasing expression of tumor-associated antigens. However, the impact of 5-Aza immune responses remains poorly understood. Here, T-cell mediated tumor immunity effects of 5-Aza, are investigated in vitro and in vivo. T-cells from healthy donors were treated with 5-Aza and analyzed by qRT-PCR and flow cytometry for changes in gene expression and phenotype. Functionality was assessed by a tumor lysis assay. Peripheral blood from patients treated with 5-Aza after alloSCT was monitored for changes in T-cell subpopulations. 5-Aza treatment resulted in a decrease in CD8+ T-cells, whereas CD4+ T-cells increased. Furthermore, numbers of IFN-γ + T-helper 1 cells (Th1) were reduced, while Treg-cells showed substantial increase. Additionally, CD8+ T-cells exhibited limited killing capacity against leukemic target cells. In vivo data confirm the increase of Treg compartment, while CD8+ T-effector cell numbers were reduced. 5-Aza treatment results in a shift from cytotoxic to regulatory T-cells with a functional phenotype and a major reduction in proinflammatory Th1-cells, indicating a strong inhibition of tumor-specific T-cell immunity by 5-Aza.

NOX-A12 is a PEGylated mirror-image oligonucleotide (a so-called Spiegelmer) that binds to CXCL12 (stromal cell-derived factor-1, SDF-1) with high affinity thereby inhibiting CXCL12 signaling on both its receptors, CXCR4 and CXCR7. In animals, NOX-A12 mobilized white blood cells (WBCs) and hematopoietic stem and progenitor cells (HSCs) into peripheral blood (PB). In healthy volunteers, single doses of NOX-A12 had a benign safety profile and also dose-dependently mobilized WBCs and HSCs into PB. HSC peak mobilization reached a plateau at five times the baseline level at an i.v. dose of 5.4 mg/kg. In accordance with the plasma half-life of 38 h, the duration of the WBC and HSC mobilization was long lasting and increased dose-dependently to more than 4 days at the highest dose (10.8 mg/kg). In conclusion, NOX-A12 may be appropriate for therapeutic use in and beyond mobilization of HSCs, e.g., in long-lasting mobilization and chemosensitization of hematological cancer cells.

Background: Soft tissue sarcomas (STS) are a highly heterogeneous group of rare malignant solid tumors. Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) comprise all STS except rhabdomyosarcoma. In patients with advanced local or metastatic disease, autologous hematopoietic stem cell transplantation (HSCT) applied after high-dose chemotherapy (HDCT) is a planned rescue therapy for HDCT-related severe hematologic toxicity., Objectives: To assess the effectiveness and safety of HDCT followed by autologous HSCT for all stages of soft tissue sarcomas in children and adults., Search Strategy: We searched the electronic databases CENTRAL (The Cochrane Library 2010, Issue 2), MEDLINE and EMBASE (February 2010). Online trial registers, congress abstracts and reference lists of reviews were searched and expert panels and authors were contacted., Selection Criteria: Terms representing STS and autologous HSCT were required in the title, abstract or keywords. In studies with aggregated data, participants with NRSTS and autologous HSCT had to constitute at least 80% of the data. Comparative non-randomized studies were included because randomized controlled trials (RCTs) were not expected. Case series and case reports were considered for an additional descriptive analysis., Data Collection and Analysis: Study data were recorded by two review authors independently. For studies with no comparator group, we synthesised results for studies reporting aggregate data and conducted a pooled analysis of individual participant data using the Kaplan-Meyer method. The primary outcomes were overall survival (OS) and treatment-related mortality (TRM)., Main Results: We included 54 studies, from 467 full texts articles screened (11.5%), reporting on 177 participants that received HSCT and 69 participants that received standard care. Only one study reported comparative data. In the one comparative study, OS at two years after HSCT was estimated as statistically significantly higher (62.3%) compared with participants that received standard care (23.2%). In a single-arm study, the OS two years after HSCT was reported as 20%. In a pooled analysis of the individual data of 54 participants, OS at two years was estimated as 49% (95% CI 34% to 64%). Data on TRM, secondary neoplasia and severe toxicity grade 3 to 4 after transplantation were sparse. All 54 studies had a high risk of bias., Authors' Conclusions: Due to a lack of comparative studies, it is unclear whether participants with NRSTS have improved survival from autologous HSCT following HDCT. Owing to this current gap in knowledge, at present HDCT and autologous HSCT for NRSTS should only be used within controlled trials.

In acute myeloid leukemia (AML), the selection of poor-risk patients for allogeneic hematopoietic stem cell transplantation (HSCT) is associated with rather high post-transplant relapse rates. As immunotherapeutic intervention is considered to be more effective before the cytomorphologic manifestation of relapse, post-transplant monitoring gains increasing attention in stem cell recipients with a previous diagnosis of AML. Different methods for detection of chimerism (e.g., microsatellite analysis or quantitative real-time PCR) are available to quantify the ratio of donor and recipient cells in the post-transplant period. Various studies demonstrated the potential use of mixed chimerism kinetics to predict relapse of the AML. CD34+-specific chimerism is associated with a higher specificity of chimerism analysis. Nevertheless, a decrease of donor cells can have other causes as well. Therefore, efforts continue to introduce minimal residual disease (MRD) monitoring based on molecular mutations in the post-transplant period. The NPM1 (nucleophosmin) mutations can be monitored by sensitive quantitative real-time PCR in subsets of stem cell recipients with AML, but for approximately 20% of patients, suitable molecular mutations for post-transplant MRD monitoring are not available so far. This emphasizes the need for an expansion of the panel of MRD markers in the transplant setting.

In recent years, the panel of known molecular mutations in acute lymphoblastic leukemia (ALL) has been continuously increased. In Philadelphia-positive ALL, deletions of the IKZF1 gene were identified as prognostically adverse factors. These improved insights in the molecular background and the clinical heterogeneity of distinct cytogenetic subgroups may allow most differentiated therapeutic decisions, for example, with respect to the indication to allogeneic HSCT within genetically defined ALL subtypes. Quantitative real-time PCR allows highly sensitive monitoring of the minimal residual disease (MRD) load, either based on reciprocal gene fusions or immune gene rearrangements. Molecular diagnostics provided the basis for targeted therapy concepts, for example, combining the tyrosine kinase inhibitor imatinib with chemotherapy in patients with Philadelphia-positive ALL. Screening for BCR-ABL1 mutations in Philadelphia-positive ALL allows to identify patients who may benefit from second-generation tyrosine kinase inhibitors or from novel compounds targeting the T315I mutation. Considering the central role of the molecular techniques for the management of patients with ALL, efforts should be made to facilitate and harmonize immunophenotyping, cytogenetics, and molecular mutation screening. Furthermore, the potential of high-throughput sequencing should be evaluated for diagnosis and follow-up of patients with B-lineage ALL.

Despite the favorable prognosis of most patients with Hodgkin's Lymphoma (HL), 15-20% of patients remain refractory to chemoradiotherapy, and 20-40% experience relapses following autologous stem cell transplantation (SCT) being used as salvage approach in this situation. Long-term survival of only 20% was reported for patients who failed this option. As some authors suggested the presence of a graft versus HL effect, allogeneic SCT was introduced as a further option. Myeloablative strategies were reported to be able to achieve cure in some younger patients, but high nonrelapse mortality remains a problem. Reduced intensity conditioning, in turn, was found to be associated with high posttransplant relapse rates. As there is currently no standard in the management of HL patients who failed autologous SCT, we here review the literature on allogeneic stem cell transplantation in HL patients with a special focus on the outcomes and risk factors being reported in the largest studies.