Transplantation and Cellular Therapy最新文献

{"title":"Masthead (Purpose and Scope)","authors":"","doi":"10.1016/S2666-6367(24)00703-6","DOIUrl":"10.1016/S2666-6367(24)00703-6","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Page A4"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Retrospective Study of Pediatric Patients With Low- or Intermediate-Risk Acute Myeloid Leukemia Who Underwent Allogeneic Hematopoietic Cell Transplantation for the AML-05 Study Conducted by the Japanese Pediatric Leukemia/Lymphoma Study Group","authors":"Yoshiko Hashii ,&nbsp;Koji Kawaguchi ,&nbsp;Hiroyuki Kurakami ,&nbsp;Katsutsugu Umeda ,&nbsp;Daiichiro Hasegawa ,&nbsp;Tomohiko Taki ,&nbsp;Nobuyuki Hyakuna ,&nbsp;Hiroyuki Ishida ,&nbsp;Yoshiyuki Takahashi ,&nbsp;Masayuki Nagasawa ,&nbsp;Hiromasa Yabe ,&nbsp;Michihiro Yano ,&nbsp;Yozo Nakazawa ,&nbsp;Hiroyuki Fujisaki ,&nbsp;Kimikazu Matsumoto ,&nbsp;Masakatsu Yanagimachi ,&nbsp;Nao Yoshida ,&nbsp;Harumi Kakuda ,&nbsp;Atsushi Satou ,&nbsp;Ken Tabuchi ,&nbsp;Koji Kato","doi":"10.1016/j.jtct.2024.08.011","DOIUrl":"10.1016/j.jtct.2024.08.011","url":null,"abstract":"<div><div>The AML-05 study aimed to examine the efficacy and safety of a therapeutic strategy based on risk stratification for low-, intermediate-, or high-risk acute myeloid leukemia (AML) pediatric patients. Allogeneic hematopoietic cell transplantation (allo-HCT) was not indicated for low- or intermediate-risk AML patients in first complete remission. The present retrospective study for the AML-05 study aimed to identify prognostic factors for survival and to determine optimal allo-HCT according to multivariate analysis on overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR), and cumulative incidence of nonrelapse mortality for and between low- and intermediate-risk AML group patients in the AML-05 study who had undergone allo-HCT after its completion and relapse. The unique patient numbers (UPNs) of the AML-05 study were matched with the Transplant Registry Unified Management Program (TRUMP)-registered numbers, and the tied data on the AML-05 study's UPNs and the TRUMP-registered numbers were analyzed. The primary endpoint was 3-yr OS. Among 443 AML patients in the AML-05 study, 79 (32 low-risk AML and 47 intermediate-risk AML) were analyzed. The following statistically favorable prognostic factors were identified by multivariate analysis on the low- and intermediate-risk AML groups, respectively: UCB (OS—hazard ratio [HR], 0.105; 95% CI, 0.011 to 0.941; <em>P</em> = .004 and EFS—HR, 0.065, 95% CI, 0.007 to 0.577, <em>P</em> = .014) and late relapse (OS—HR, 0.212; 95% CI, 0.072 to 0.626; <em>P</em> = .005 and EFS—HR, 0.236; 95% CI, 0.088 to 0.630; <em>P</em> = .004). Three-year OS, 3-yr EFS, and 3-yr CIR were significantly different between the low- and intermediate-risk AML groups. UCB may be a safe and beneficial donor source for low-risk AML patients, while late relapse was a favorable prognostic factor for intermediate-risk AML patients. Intermediate-risk AML patients with late relapse and low-risk AML patients may benefit from allo-HCT after relapse.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1102.e1-1102.e12"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypomethylating Agents are Effective in Treatment for Relapsed Myelofibrosis After Allogeneic Hematopoietic Cell Transplantation","authors":"Dat Ngo ,&nbsp;Jose Tinajero ,&nbsp;Abdullah Ladha ,&nbsp;Monzr M. Al Malki ,&nbsp;Salman Otoukesh ,&nbsp;Idoroenyi Amanam ,&nbsp;Haris Ali","doi":"10.1016/j.jtct.2024.08.013","DOIUrl":"10.1016/j.jtct.2024.08.013","url":null,"abstract":"<div><div>Myelofibrosis (MF) is a myeloproliferative neoplasm with a relapse rate of 10% to 30% after allogeneic transplantation (alloHCT). Current recommendations to treat relapse include withdrawal of immunosuppression, donor lymphocyte infusion, and potentially a second alloHCT. Hypomethylating agents (HMAs) have shown efficacy as salvage therapy by inducing an immune response and improving donor chimerism for myeloid neoplasm post-HCT. Data is limited on use of HMAs for MF post-alloHCT relapse. To determine the benefit of using HMAs for MF patients relapsing after alloHCT, we retrospectively analyzed 12 patients with MF post-alloHCT relapse who received HMA to determine response via restoration of donor chimerism and clearance of molecular mutation. The median age was 61 years (range 41-72) with 92% classified as intermediate-2/high-risk by the Dynamic International Prognostic Scoring System (DIPSS) and 83% as high/very high risk by the MIPSS70+ (Molecular International Prognostic Scoring System). The median time to relapse post-alloHCT was 282.5 days (range 96-2388) with median donor chimerism 57.82% (range 2.48-84.0) prior to starting an HMA. After two cycles of HMA, 58% experienced restoration of donor chimerism. Molecular clearance of pre-HCT driver mutations occurred in 50% of patients at the most recent follow-up. New chronic graft-vs.-host disease (cGVHD) occurred in 50% of patients, with most being mild to moderate that resolved after treatment. HMA was safe and effective in a high-risk population after post-alloHCT relapse and is an option for patients in the future.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1091.e1-1091.e8"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preadmission Penicillin Allergy Evaluation Before Hematopoietic Stem Cell Transplantation Optimizes Febrile Neutropenia Treatment and Inpatient Resource Utilization","authors":"George X. Huang ,&nbsp;Lauren E. Merz ,&nbsp;Geneva D. Mehta ,&nbsp;Kathleen D. Marquis ,&nbsp;Kylie Besz ,&nbsp;Donna-Marie Lynch ,&nbsp;Corey Cutler ,&nbsp;Mariana C. Castells","doi":"10.1016/j.jtct.2024.08.021","DOIUrl":"10.1016/j.jtct.2024.08.021","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Febrile neutropenia is a common complication of conditioning chemotherapy for hematopoietic stem cell transplant (HSCT), but a major barrier for optimal treatment of febrile neutropenia is historical penicillin allergies. Our group recently published a development of a clinical pipeline for delabeling penicillin allergies in adult patients planned to undergo hematopoietic stem cell transplant (HSCT). In this retrospective cohort study, we followed patients to evaluate their outcomes during inpatient admission for HSCT. We hypothesized that, among patients planned for HSCT with a self-reported penicillin allergy, completing penicillin allergy testing (amoxicillin ingestion challenge with or without concomitant penicillin skin testing) prior to HSCT admission would be associated with differences in inpatient treatment for febrile neutropenia (including antibiotic selection and timing of antibiotic administration) and improved inpatient resource utilization (including nursing and inpatient physician consults). We identified patients with a self-reported penicillin allergy who answered a penicillin allergy questionnaire and were subsequently admitted to our institution for HSCT. We divided the cohort into 2 groups: patients whose penicillin allergy was evaluated prior to admission (EPTA) and patients whose penicillin allergy was not evaluated prior to admission (NEPTA). We then performed comparison between the 2 groups for general clinical outcomes of HSCT admission (duration of admission, need for ICU transfer, readmission rate, etc.), febrile neutropenia treatment, and inpatient resource utilization. Statistics were calculated using the nonparametric 2-tailed Fisher exact test for categorical outcomes and the nonparametric 2-tailed Mann-Whitney U test for numerical outcomes. Within our cohort, 35 patients completed penicillin allergy testing prior to HSCT admission (EPTA) and 44 patients did not (NEPTA). Demographics were similar between these groups, and there was no significant difference in the rate of febrile neutropenia during HSCT admission (EPTA 64% versus NEPTA 66%, &lt;em&gt;P&lt;/em&gt; = 1.00). EPTA patients were significantly more likely to receive standard first-line antibiotics (cefepime or ceftazidime) for febrile neutropenia (EPTA 95% versus NEPTA 65%, &lt;em&gt;P&lt;/em&gt; = .015) and time between febrile neutropenia onset and antibiotic administration was shorter (EPTA mean 66 mins versus NEPTA mean 121 mins, &lt;em&gt;P&lt;/em&gt; = .0058). No patients in the EPTA group experienced an immediate hypersensitivity reaction (hives, anaphylaxis, etc.) or severe cutaneous adverse reaction (SCAR) during HSCT admission. EPTA patients were also significantly less likely to require 1:1 nursing for antibiotic test doses, challenges, and desensitizations (EPTA 0% versus NEPTA 49%, &lt;em&gt;P&lt;/em&gt; &lt; .0001); less likely to require inpatient allergy consult (EPTA 0% versus NEPTA 12%, &lt;em&gt;P&lt;/em&gt; = .031); and less likely to require inpatient antimicrobial stewardship consu","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1112.e1-1112.e9"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Outcomes of Upfront Autologous Hematopoietic Stem Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma With Deletion 17p.","authors":"Curtis Marcoux, Oren Pasvolsky, Denái R Milton, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Hans C Lee, Krina K Patel, Partow Kebriaei, Amna Ahmed, Yosra Aljawai, Sheeba K Thomas, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash","doi":"10.1016/j.jtct.2024.10.011","DOIUrl":"10.1016/j.jtct.2024.10.011","url":null,"abstract":"<p><p>Despite tremendous advancements in multiple myeloma (MM) therapeutics, outcomes remain heterogeneous, heavily influenced by clinical and cytogenetic factors. Among these, deletion of the short arm of chromosome 17 (del(17p)) is a strong predictor of poor prognosis. The aim of this study was to evaluate real-world outcomes in patients with newly diagnosed MM (NDMM) with del(17p) undergoing upfront autologous hematopoietic stem cell transplantation (auto-HCT). We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-HCT at MD Anderson Cancer Center between 2008 and 2018. Primary endpoints were progression-free survival (PFS) and overall survival (OS), with secondary endpoints being hematological response and measurable residual disease (MRD) status postauto-HCT. MRD status in the bone marrow biopsy was evaluated using 8-color next-generation flow cytometry with a sensitivity of 1/10^-5 cells. One hundred and fifteen patients were included (55% male). Median age at auto-HCT was 62 years (range 34 to 83). The median del(17p) clone size was 20%, with 51 (53%) patients having clone sizes >20% and 15 (15%) patients having clone sizes >55%. Additional high-risk cytogenetic abnormalities included t(4;14) in 15 (13%) patients, t(14;16) in 8 (7%) patients, and 1q21+ in 25 (22%) patients. After induction, 10% of patients achieved ≥ CR, and 50% achieved ≥ VGPR, with 25% having MRD-negative ≥ VGPR. Post-transplant, 42% achieved ≥ CR, and 83% achieved ≥ VGPR as best response, with 55% (48/87) having MRD-negative ≥ VGPR. With a median follow-up of 31.4 months (range 3.1 to 199.1), median PFS and OS for the entire cohort were 19.9 and 71.5 months, respectively, and 5-year OS was 53%. Concurrent del(17p) and t(4;14) were associated with significantly worse outcomes, with median PFS and OS of 11.5 and 22.4 months, respectively. In multivariable analysis (MVA), female sex was associated with worse PFS (HR [95% CI] 2.87 [1.75 to 4.72], P < .001), while MRD negative CR post-transplant (0.35 [0.18 to 0.68], P = .002) and maintenance therapy (0.46 [0.27 to 0.77], P = 0.003) were associated with better PFS. In MVA for OS, female sex (2.22 [1.18 to 4.17], P = 0.013) and the presence of t(4;14) (2.55 [1.09 to 5.95], P = 0.030) were associated with worse OS, whereas Karnofsky Performance Status of ≥90 (0.47 [0.23 to 0.94], P = 0.034) was associated with better OS. This study affirms del(17p) as a high-risk abnormality with unfavorable outcomes despite modern therapies. The co-occurrence of del(17p) and t(4;14) was associated with particularly poor outcomes. Novel approaches are needed for this high-risk subgroup.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shift from Widespread to Tailored Antifungal Prophylaxis in Lymphoma Patients Treated with CD19 CAR T Cell Therapy: Results from a Large Retrospective Cohort.","authors":"Giovanna Melica, Alejandro Luna de Abia, Gunjan L Shah, Sean Devlin, Magdalena Corona, Joshua Fein, Parastoo B Dahi, Sergio A Giralt, Richard J Lin, M Lia Palomba, Allison Parascondola, Jae Park, Gilles Salles, Amethyst Saldia, Michael Scordo, Roni Shouval, Miguel-Angel Perales, Susan K Seo","doi":"10.1016/j.jtct.2024.10.010","DOIUrl":"10.1016/j.jtct.2024.10.010","url":null,"abstract":"<p><p>Patients undergoing CD19 chimeric antigen receptor (CAR)-T cell therapy exhibit multiple immune deficits that may increase their susceptibility to infections. Invasive fungal infections (IFIs) are life-threatening events in the setting of hematologic diseases. However, there is ongoing debate regarding the optimal role and duration of antifungal prophylaxis in this specific patient population. The objective of this study was to provide a comprehensive overview of the evolution of IFI prophylactic strategies over time and to assess IFI incidence rates in a cohort of patients with relapsed or refractory (R/R) lymphoma treated with CAR-T cell therapy. A single-center retrospective study was conducted on a cohort of patients with R/R B cell lymphoma treated with CD19 CAR-T cell therapy between April 2016 and March 2023. Group A (April 2016-August 2020) consisted of patients primarily treated with fluconazole, irrespective of their individual IFI risk profile. In Group B (September 2020-March 2023) antifungal prophylaxis was recommended only for high-risk patients. Overall, 330 patients were included. Antifungal prophylaxis was prescribed to 119/142 (84%) patients in Group A and 58/188 (31%) in Group B (P < .001). Anti-mold azoles were prescribed to 8 (5.6%) patients in Group A and 21 (11.2%) patients in Group B. In Group A, 42 (29%) patients were switched to another antifungal, 9 (21%) because of toxicity, with 6 cases of transaminitis and 3 cases of prolonged QTc. In Group B, 21 (11.2%) patients were switched to the antifungal drug, mainly from fluconazole or micafungin to a mold-active agent following revised guidelines. No difference was found in liver toxicity between the two groups at infusion, day 10, and day 30. No significant differences were observed between the groups. IFIs following CAR-T cell therapy were rare, with 1 case of cryptococcal meningoencephalitis in group A (.7%) and 1 case of invasive aspergillosis in Group B (.5%), both occurring in patients on micafungin prophylaxis. In this large single-center cohort of patients with R/R lymphoma treated with CAR-T cells, we show that individualized prophylaxis, alongside careful management of CAR-T cell-related toxicities such as CRS, was associated with a very low IFI rate, avoiding the risk of unnecessary toxicities, drug-drug interactions, and high costs.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastric Bleeding in Stem Cell Transplantation: A Focus on Gastric Vascular Ectasia Under Post-Transplant Cyclophosphamide, Sirolimus, and Mycophenolate Mofetil Prophylaxis.","authors":"Juan Eirís, Juan Montoro, Marta Villalba, Pedro Chorão, Marina Pérez-Bravo, Nuria Rausell, Carla Satorres, Pedro Asensi Cantó, Inés Gómez-Seguí, Pilar Solves, Marta Santiago, Pilar Lloret-Madrid, Pablo Granados, David Martínez-Campuzano, Rafael Benavente, Alberto Louro, Paula Rebollar, Aurora Perla, Miguel A Sanz, Javier de la Rubia, Aitana Balaguer-Roselló, Jaime Sanz","doi":"10.1016/j.jtct.2024.10.009","DOIUrl":"10.1016/j.jtct.2024.10.009","url":null,"abstract":"<p><p>Gastrointestinal bleeding (GIB) is a serious complication following allogeneic hematopoietic stem cell transplantation (HSCT), with limited data on its incidence and characteristics, particularly for upper gastrointestinal bleeding (UGIB) of gastric origin. We aimed to evaluate the incidence, clinical, endoscopic, and histopathologic features, and outcomes of UGIB, with a focus on gastric vascular ectasias (GVEs) in patients undergoing HSCT with graft-versus-host disease (GVHD) prophylaxis using post-transplant cyclophosphamide (PTCY), sirolimus or calcineurin inhibitors, and mycophenolate mofetil. This retrospective, single-center study included all adult patients who underwent allogeneic HSCT at a single institution between January 2017 and December 2023. Data were collected on transplant procedures, complications, and GIB incidents, with UGIB cases undergoing endoscopic and histologic examination. Out of 559 patients, 38 (6.6%) experienced UGIB, with 27 cases (70%) attributed to GVE. GVE typically presented as melena or hematemesis at a median time of 68 d (range, 29 to 125) after transplant. Endoscopy revealed diffuse oozing from gastric antral mucosa without distinct lesions, while histology showed vascular congestion and mild foveolar hyperplasia. The 6-mo cumulative incidence of GVE was 5.1%. Older age (≥60 yr) and diagnosis of myelodysplastic/myeloproliferative neoplasm were significant risk factors. All cases resolved with no attributable mortality with supportive measures including transfusions, proton-pump inhibitors, and sirolimus withdrawal in some cases. GVE is a notable cause of UGIB in HSCT recipients on PTCY-based GVHD prophylaxis, presenting significant morbidity but favorable outcomes with appropriate management. The potential role of sirolimus and conditioning agents in GVE pathogenesis warrants further investigation.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pilot Study of UM171-Expanded Cord Blood Grafts for Tandem Auto/Allogeneic Hematopoietic Cell Transplant in High and Ultra-High-Risk Myeloma Patients.","authors":"Jean Roy, Sandra Cohen, Guy Sauvageau, Imran Ahmad, Valentyn Fournier, Rafik Terra, Pierre Caudrelier, Stéphanie Thiant, Gabrielle Thauvette, Nadia Bambace, Jean-Sébastien Delisle, Silvy Lachance, Thomas Kiss, Léa Bernard, Denis Claude Roy, Olivier Veilleux, Richard LeBlanc","doi":"10.1016/j.jtct.2024.10.008","DOIUrl":"10.1016/j.jtct.2024.10.008","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Multiple myeloma (MM) remains associated with a poor outcome, particularly in patients with advanced disease and high-risk (HR) cytogenetics. To date, the only curative treatment is allogeneic (allo) hematopoietic cell transplantation (HCT), but high incidences of graft versus host disease (GVHD), nonrelapse mortality (NRM) and disease progression remain important obstacles. Cord blood (CB) transplantation has been associated with low rates of relapse and chronic (c) GVHD, but its use has declined because of high incidences of infections, severe acute GVHD and high NRM. In other hematologic malignancies, UM171-expanded CB transplants have led to improved outcomes, allowing for the selection of smaller, better HLA-matched units. We aimed to investigate the safety and feasibility of single UM171-expanded single CB unit transplantation in frontline tandem auto/allo HCT for HR/ultra-HR MM patients. Newly diagnosed MM patients ≤ 65 years with an ISS stage II/III and del(17p), t(4;14), t(14;16), t(14;20), del(1p) or +1q, R-ISS 3, ≥ 2 cytogenetic abnormalities, or plasma cell leukemia without a sibling donor and availability of a 5-7/8 matched CB graft with ≥ 0.5 x 10&lt;sup&gt;5&lt;/sup&gt; CD34+/kg and ≥ 1.5 x 10&lt;sup&gt;7&lt;/sup&gt; TNCs/kg were eligible to this phase I/II prospective study (ClinicalTrials.gov NCT03441958). After induction and autologous HCT, patients received a reduced intensity conditioning regimen and were infused with 7-day UM171-expanded CD34+ cells, along with the lymphocytes contained in the CD34-negative fraction. The primary endpoints were feasibility of UM171 expansion, safety, kinetics of engraftment, incidences and maximum grades of acute and cGVHD at 1 and 2 years, assessment of measurable residual disease (MRD) and quality of life (QoL). Between 05/2018 and 11/2021, 20 patients were enrolled. One patient had an unsuccessful CB expansion with UM171, leaving 19 patients with a median age of 56 years. Median CD34+ cell dose infused after expansion was 4.62 x 10&lt;sup&gt;6&lt;/sup&gt;/kg (range: 0.79 to 5.76). Median times to achieve absolute neutrophil counts of 0.1 and 0.5 x 10&lt;sup&gt;9&lt;/sup&gt;/L were D+6 and D+10.5; median time to reach ≥ 20 x 10&lt;sup&gt;9&lt;/sup&gt;/L platelets was D+36. Full donor chimerism was achieved in all cell lineages by D+120 in recipients of reduced intensity conditioning. Cumulative incidences of grade II-IV, grade III-IV acute GVHD and moderate/severe cGVHD at 12 months were 68.4% (95% CI: 46 to 90), 5.3% (95% CI: 0% to 16%), and 10.5% (95% CI: 0% to 25%), respectively. With a median follow-up of 2.9 years (range: 0.46 to 5.3), cumulative incidences of relapse, PFS, OS and NRM at 3 years were 36.8% (95% CI: 14 to 59), 47.4% (95% CI: 29 to 76), 68.4% (95% CI: 50 to 93) and 15.8% (95%CI: 0 to 33), respectively. Median time to complete immunosuppression discontinuation was D+238. No unexpected adverse events were observed. Only one of 7 patients alive at 2 years with negative MRD at transplant has relapsed. Non-relapsing patients had ","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total Marrow and Lymphoid Irradiation (TMLI) Is Associated with Good Early Outcomes in Patients Undergoing Matched Sibling Donor and Haplo-identical Transplants for Acute Lymphoblastic Leukemia.","authors":"Yamuna Naik, Uday Kulkarni, Sharon Lionel, Sushil Selvarajan, Anup J Devasia, Anu Korula, Kavitha M Lakshmi, Fouzia N Aboobacker, Rajesh Balakrishnan, Selvamani Backianathan, Vikram Mathews, Aby Abraham, Biju George","doi":"10.1016/j.jtct.2024.10.007","DOIUrl":"10.1016/j.jtct.2024.10.007","url":null,"abstract":"<p><p>Total marrow and lymphoid irradiation (TMLI) can deliver higher doses of irradiation without increased toxicity. This study evaluated TMLI and cyclophosphamide in patients undergoing stem cell transplantation for acute lymphoblastic leukemia (ALL). A total of 58 patients underwent matched related, unrelated, or haplo-identical donor transplantation using TMLI. The graft source was peripheral blood stem cells (PBSCs) in ALL whereas graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine with methotrexate or post-transplant cyclophosphamide. The median age was 20 years (range: 5-49 years) and included 20 children. Engraftment occurred in 56 (96.5%) at a median of 15 days (range: 12-23) with 2 early deaths. Sinusoidal obstruction syndrome (SOS) was seen in 10 patients whereas hemorrhagic cystitis and cardiac dysfunction occurred in 2 patients each. Cumulative incidence (CI) of grades II-IV acute GVHD was 23.6% whereas the CI of grades III-IV was 10.9%. Chronic GVHD was seen in 46.9% whereas relapse was seen in 10 patients (17.2%). The 2-year overall survival (OS) was 65.9% ± 6.8% and the 2-year disease-free survival (DFS) was 59% ± 6.7%. Outcomes were compared with 52 patients who received either Cy/TBI or Flu/Bu4 for conditioning during the same period. Engraftment rates and time to engraftment were similar. Acute GVHD (P = .002), regimen-related toxicity (P = .043) and day 100 non-relapse mortality (P = .020) were significantly lower with TMLI. TMLI was associated with better OS (P = .004) and DFS (P = .005) for haplo-identical transplants. Better DFS was seen with TMLI in patients with high-risk disease (P = .007) and disease status > CR1 (P = .041). The use of TMLI and cyclophosphamide is associated with good outcomes in patients undergoing hematopoietic stem cell transplantation for ALL, especially with haplo-identical stem cell transplants.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequential Conditioning With FLAMSA Does Not Improve Outcomes of Allogeneic Stem Cell Transplantation in Chronic Myelomonocytic Leukemia Patients.","authors":"Radwan Massoud, Evgeny Klyuchnikov, Normann Steiner, Gaby Zeck, Silke Heidenreich, Claudia Langebrake, Christian Niederwieser, Kristin Rathje, Nico Gagelmann, Dietlinde Janson, Christine Wolschke, Francis Ayuk, Nicolaus Kröger","doi":"10.1016/j.jtct.2024.10.003","DOIUrl":"10.1016/j.jtct.2024.10.003","url":null,"abstract":"<p><p>As with myelodysplastic syndromes (MDS), effective treatment options for chronic myelomonocytic leukemia (CMML) are limited, and the optimal treatment approach remains undefined. Allogeneic stem cell transplantation (allo-SCT) is potentially curative therapy for patients with CMML. Sequential conditioning with FLAMSA was initially developed for refractory acute myeloid leukemia and has since been applied in the treatment of MDS and CMML. Data on optimal allo-SCT conditioning in CMML Patients is scarce. This retrospective study from the Department of Stem Cell Transplantation at the University Medical Center Hamburg, Germany, compared allo-SCT outcomes in CMML patients across three conditioning regimes: Thiotepa-busulfan (TB), sequential FLAMSA-busulfan fludarabine (FLAMSA-FB), and treosulfan-fludarabine (Treo-Flu). Sixty-nine consecutive patients with CMML who underwent allo-SCT between the years 2006 and 2022 were included in the study. Twenty-two received TB, 27 received FLAMSA-FB, and 20 received Treo-Flu conditioning. Transplant sources included matched related donors (8 patients), mismatched related donors (8 all in the TB group), matched unrelated donors (31), and mismatched unrelated donors (22) with significant group variations (P < .001). Most patients received anti-T lymphocyte Globulin for graft versus host disease (GVHD) prophylaxis (TB 68%, FLAMSA-FB 93%, Treo-Flu 85%, P = .08). CPSS-Molecular score was comparable between the groups. One TB patient experienced primary graft failure, but engraftment times were comparable across the groups. Although not statistically significant, the TB group showed a trend toward improved 3-year overall survival (OS) rates (80%) compared to FLAMSA-FB (37%) and Treo-Flu (55%) (P = .05). The TB group also displayed significantly higher 3-year progression-free survival (PFS) rates (80%) compared to FLAMSA-FB (33%) and Treo-Flu (both 39%), (P = .02). No significant differences were observed in 3-year non-relapse mortality across the TB (20%), FLAMSA-FB (30%), and Treo-Flu (26%) groups (P = .8). Interestingly, no TB patients relapsed at 3 years, contrasting with the FLAMSA-FB (41%) and Treo-Flu groups (30%, P = .02). Lastly, cumulative incidences of acute and chronic GVHD were similar across groups. Our analysis suggests FLAMSA-FB does not improve transplant outcomes, however, TB represents the preferred conditioning regimen for CMML patients undergoing allo-SCT. It demonstrates notable advantages in relapse prevention and leads to improved OS and PFS compared to FLAMSA-FB and Treo-Flu protocols.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}