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 × 106/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.

• MeSH
• Survival Analysis MeSH
• Databases, Factual MeSH
• Adult MeSH
• Histocompatibility * MeSH
• Transplantation, Homologous MeSH
• Middle Aged MeSH
• Humans MeSH
• Graft vs Host Disease MeSH
• Graft Survival MeSH
• Primary Myelofibrosis mortality   therapy   MeSH
• Transplantation Conditioning MeSH
• Recurrence MeSH
• Retrospective Studies MeSH
• Family * MeSH
• Aged MeSH
• Societies, Medical MeSH
• Hematopoietic Stem Cell Transplantation methods   MeSH
• Bone Marrow Transplantation statistics & numerical data   MeSH
• Peripheral Blood Stem Cell Transplantation statistics & numerical data   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

Léčba T-lymfocyty modifikovanými chimérickým antigenním receptorem (CART) je pro pacienty s relabující/refrakterní B-buněčnou akutní lymfoblastickou leukemií (r/r B-ALL) účinná a bezpečná, ale s ohledem na dlouhodobé přežívání bez leukemie je její význam omezený. Je tudíž potřeba mít k dispozici nové postupy, které podpoří dlouhodobou účinnost terapie CART. Tato nerandomizovaná, intervenční, pragmatická studie měla specifický cíl. Prozkoumali jsme, zda může konsolidační alogenní transplantace hematopoetických kmenových buněk (allo-HSCT – allogeneic hematopoietic stem cell transplantation) zlepšit dlouhodobou prognózu pacientů dosáhnuvších kompletní remise s negativitou minimální reziduální nemoci (MRD− CR – minimal residual disease-negative complete remission) po léčbě CART. V prvním stadiu dostalo 58 pacientů s r/r B-ALL po lymfodepleční chemoterapii CAR T-lymfocyty v samostatných dávkách a 51 (87,9 %) z nich dosáhlo CR. Ve druhém stadiu dostalo 21/47 pacientů s MRD− CR bez předchozí allo-HSCT a bez kontraindikací či dalších omezení do 3 měsíců po léčbě CART na základě jejich souhlasu konsolidační allo-HSCT. U pacientů s MRD− CR nebyl mezi těmi, jimž byla provedena allo-HSCT, a těmi bez allo-HSCT žádný rozdíl v celkovém přežívání (OS – overall survival). Avšak přežívání bez příznaku zhoršení nemoci (EFS – event-free survival) a přežívání bez relapsu (RFS – relapse-free survival) se v podskupinách s allo-HSCT signifikantně prodloužila. Týkalo se to pacientů buď s vysokou (≥ 5 %) MRD v kostní dřeni před infuzí stanovenou průtokovou cytometrií (BM-FCM-MRD – bone marrow-fl ow cytometry-minimal residual disease), nebo s nepříznivými prognostickými markery (P < 0,05). U pacientů s BM-FCM-MRD < 5 % a bez nepříznivých prognostických markerů (P > 0,05) však nebyl v EFS a RFS zaznamenán žádný rozdíl. Lze uzavřít, že přemosťující terapie CART před allo-HSCT je pro pacienty s r/r B-ALL bezpečnou a účinnou léčebnou strategií, která může prodloužit EFS a RFS, zejména pokud mají před infuzí vysokou BM-FCM-MRD nebo nepříznivé prognostické markery.

• MeSH
• Survival Analysis MeSH
• Antigens, CD19 MeSH
• Adult MeSH
• Transplantation, Homologous methods   statistics & numerical data   MeSH
• Immunotherapy, Adoptive * methods   adverse effects   statistics & numerical data   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymphocyte Depletion methods   statistics & numerical data   MeSH
• Young Adult MeSH
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma * immunology   therapy   MeSH
• Transplantation Conditioning methods   MeSH
• Neoplasm, Residual immunology   therapy   MeSH
• Statistics as Topic MeSH
• Hematopoietic Stem Cell Transplantation methods   statistics & numerical data   MeSH
• Peripheral Blood Stem Cell Transplantation methods   statistics & numerical data   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Publication type
• Pragmatic Clinical Trial MeSH

• MeSH
• Anemia, Aplastic surgery   mortality   MeSH
• Tissue Donors MeSH
• Child MeSH
• Adult MeSH
• Histocompatibility MeSH
• Evaluation Studies as Topic MeSH
• Transplantation, Homologous statistics & numerical data   MeSH
• Kaplan-Meier Estimate MeSH
• Karnofsky Performance Status MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Graft vs Host Disease MeSH
• Organ Specificity MeSH
• Child, Preschool MeSH
• Graft Survival MeSH
• Transplantation Conditioning methods   MeSH
• Proportional Hazards Models MeSH
• Registries MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Bone Marrow Transplantation statistics & numerical data   adverse effects   MeSH
• Peripheral Blood Stem Cell Transplantation statistics & numerical data   adverse effects   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Overall MeSH