This is a report of 148 patients with hematologic malignancies who received an unmanipulated haploidentical bone marrow transplant (BMT), followed by post-transplant high-dose cyclophosphamide (PT-CY). All patients received a myeloablative conditioning consisting of thiotepa, busulfan, fludarabine (n = 92) or TBI, fludarabine (n = 56). The median age was 47 years (17-74); 47 patients were in first remission (CR1), 37 in second remission (CR2) and 64 had an active disease; all patients were first grafts. The diagnosis was acute leukemia (n = 75), myelodisplastic syndrome (n = 24), myelofibrosis (n = 16), high-grade lytmphoma (n = 15) and others (n = 18). GVHD prophylaxis consisted in PT-CY on days +3 and +5, cyclosporine (from day 0), and mycophenolate (from day +1). The median day for neutrophil engraftment was day +18 (13-32). The cumulative incidence of grades II-IV acute GVHD was 24%, and of grades III-IV GVHD 10%. The incidence of moderate-severe chronic GVHD was 12%. With a median follow-up for the surviving patients of 313 days (100-1162), the cumulative incidence of transplant-related mortality (TRM) is 13%, and the relapse-related death is 23%. The actuarial 22 months overall survival is 77% for CR1 patients, 49% for CR2 patients and 38% for patients grafted in relapse (P o0.001). Major causes of death were relapse (22%), GVHD (2%) and infections (6%). We confirm our initial results, suggesting that a myeloablative conditioning regimen followed by unmanipulated haploidentical BMT with PT-CY, results in a low risk of acute and chronic GVHD and encouraging rates of TRM and overall survival, also for patients with active disease at the time of transplant.Bone Marrow Transplantation (2015) 50, S37-S39; doi:10.1038/bmt.2015.93 PATIENTS AND METHODSClinical characteristics are outlined in Table 1. All patients received a myeloablative regimen with post-transplant cyclophosphamide, between august 2010 and January 2014. A total of 64 patients had an active disease at transplant; 46 were in first remission (CR1) and 39 in second remission (CR2) hematologic remission. The most common diagnosis was acute leukemia (n = 76 ), 48 AML (27% with active disease) and 24 ALL (32% with active disease). Most of the patients with non-Hodgkin lymphoma (60%) also had advanced disease, as well as patients with myelofibrosis. DonorsAll donor/patient pairs were genotypically haplomismatched. A single patient, because of HLA homozigosity, had 0 mismatches in the graft vs host direction and three mismatched in the host vs graft direction. Conditioning regimenThe myeloablative conditioning regimen was based either on chemotherapy-thiotepa, busulfan, fludarabine-or TBI and fludarabine: 92 patients received the thiotepa, busulfan, fludarabine regimen which included thiotepa 5 mg/kg on days − 6 and − 5 (total dose 10 mg/kg), fludarabine 50 mg/m 2 on days − 4, − 3 and − 2 (total dose 150 mg/m 2 ), and busulfan 3,2 mg/kg IV on days − 4, − 3, − 2 (total dose 9,6 mg/kg). Fifty-six patients received the TBI and fludarabine regimen, which incl...
SummaryWe assessed WT1 expression (expressed as messenger copies/10 4 ABL1) from marrow cells of 122 patients with acute myeloid leukaemia (AML), before and after an unmanipulated allogeneic haemopoietic stem cell transplant (HSCT). The median age was 44 years (15-69), 59% were in first remission, 74% received a myeloablative conditioning regimen and the median follow up was 865 d (34-2833). Relapse was higher in 67 patients with WT1 expression, at any time post-HSCT, exceeding 100 copies (54%), as compared to 16%, for 55 patients with post-HSCT WT1 expression <100 copies (P < 0Á0001). Similarly, actuarial 5-year survival (OS) was 40% vs. 63%, respectively (P = 0Á03). In multivariate Cox analysis, WT1 expression post-HSCT was the strongest predictor of relapse (Hazard Ratio [HR] 4Á5, P = 0Á0001), independent of disease phase (HR 2Á3, P = 0Á002). Donor lymphocyte infusions (DLI) were given to 17 patients because of increasing WT1 levels: their OS was 44%, vs. 14% for 21 patients with increasing WT1 expression who did not receive DLI (P = 0Á004). In conclusion, WT1 expression post-HSCT is a strong predictor of leukaemia relapse and survival in AML; WT1 may be used as a marker for early interventional therapy.
Forty-two patients relapsing after an unmanipulated haploidentical BM transplant and post-transplant CY (PT-CY), were given 108 DLI, with median interval from transplant of 266 days (range, 67-1372). DLI were given at escalating doses, expressed as CD3+ cells/kg, without GVHD prophylaxis, and ranged from 1 × 10 3 to 1 × 10 7 cells/kg (median 5 × 10 5 cells/kg). The average number of DLI per patient was 2.6 (range, 1-6). The diagnosis was leukemias (n = 32) grafted with a myeloablative regimen and Hodgkin's disease (n = 10), grafted with a nonmyeloablative regimen. Leukemic patients with molecular relapse (n = 20), received DLI alone (n = 17) or in association with azacytidine (n = 3); leukemic patients with hematologic relapse (n = 12) received chemotherapy followed by DLI (n = 11) or DLI alone (n = 1); Hodgkin patients received DLI following 1-3 courses of chemotherapy. In these three groups the incidence of acute GVHD II-III was 15%, 17% and 10%; response rate was 45%, 33% and 70%; 2-year actuarial survival was 43%, 19% and 80% respectively. This study confirms that escalating doses of DLI can be given in the haploidentical setting with PT-CY, with a relatively low risk of acute GVHD. Response rates and survival are dependent on the underlying disease.
Minimal residual disease (MRD) was monitored by Wilms tumor 1 (WT1) expression in 207 patients with acute myeloid leukemia (AML) after an allogeneic hemopoietic stem cell transplantation (HSCT) as a trigger to initiate pre-emptive immunotherapy (IT) with cyclosporin discontinuation and/or donor lymphocyte infusion. The trigger for IT was WT1 ≥ 180 copies/10(4) Abelson cells in marrow cells in the first group of 122 patients (WT1-180) and ≥ 100 copies in a subsequent group of 85 patients (WT1-100). Forty patients received IT. The cumulative incidence (CI) of relapse was 76% in WT1-180 (n = 17) versus 29% in WT1-100 patients (n = 23) receiving IT (P = .006); the leukemia-free survival from MRD positivity was 23% versus 74%, respectively (P = .003). We then looked at the entire AML patient population (n = 207). WT1-180 and WT1-100 patients were comparable for disease phase and age. The overall 4-year CI of transplantation-related mortality was 13% in both groups; the CI of leukemia relapse was 38% in the WT1-180 and 28% in the WT1-100 patients (P = .05) and leukemia-free survival was 56% versus 48%, respectively (P = .07). In conclusion, we suggests that WT1-based pre-emptive immunotherapy is feasible in patients with undergoing an allogeneic HSCT. The protective effect on relapse is greater when IT is triggered at lower levels of WT1.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.