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New-onset post-transplant diabetes mellitus after haploidentical hematopoietic cell transplant with post-transplant cyclophosphamide.

ABSTRACT: Haploidentical hematopoietic cell transplant (haplo-HCT) with post-transplant cyclophosphamide (PTCY) is utilized for patients with hematological disorders but without conventional donors. The effects of new-onset post-transplant diabetes mellitus (PTDM) following haplo-HCT are unknown. We examined PTDM incidence and outcomes after haplo-HCT with PTCY. Patients without diabetes receiving haplo-HCT (n=64) were analyzed for PTDM diagnosis (defined as blood glucose≥ 200 mg/dL). By day 100, 14 (22%) patients developed PTDM (median, 18 days). Hyperglycemia (blood glucose ≥ 200 mg/dL) preceded corticosteroids in 11 (79%) individuals. PTDM patients had increased death/relapse (p=0.029). PTDM occurs frequently, precedes corticosteroids, and leads to inferior outcomes following haplo-HCT. PTDM prophylaxis/treatment may improve HCT survival.

SUBMITTER: Mangan BL

PROVIDER: S-EPMC7942195 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Aims and objectivesHaploidentical transplants constitute a potential alternative therapy for patients who urgently need transplantation in the absence of human leukocyte antigen-matched donors. We report a single-center experience regarding the initial results of haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) using post-transplant cyclophosphamide (PTCy) at the HCMC Blood Transfusion Hematology (BTH) Hospital.MethodsWe conducted a retrospective case series study of 23 patients who underwent haplo-PBSCT using PTCy at the HCMC BTH Hospital between January 2014 and January 2021. The refined disease risk index (DRI) was used to stratify the outcomes. We evaluated the engraftment rate, graft-versus-host disease (GVHD), and complications during haploidentical transplantation. Overall survival (OS), disease-free survival (DFS), and GVHD-free relapse-free survival (GRFS) were assessed.ResultsThe majority of the patients in the present study were diagnosed with acute myeloid leukemia. All patients received reduced-intensity conditioning regimens. The engraftment rate was 86.9%. The median times to neutrophil and platelet engraftment were 17 and 31 days, respectively. Two patients (8.7%) reported severe acute GVHD (grade III-IV), while two patients (8.7%) had grade I-II acute GVHD. Three patients experienced limited chronic GVHD of the skin, requiring topical steroids. The most common complication was bloodstream infection (60.9%). Cytomegalovirus reactivation occurred in 19 patients (82.6%) and 17.4% developed hemorrhagic cystitis. The 1-year relapse rate was 32.5%. The cumulative incidence of non-relapse mortality at 1 year was 17.3%. The 1-year OS and DFS rates were 66.3% and 55.7%, respectively. The 1-year GRFS rate was 49.2%. A high/very high DRI score was associated with worse OS after haplo-PBSCT (P=0.038).ConclusionHaploidentical transplant using PTCy is a feasible therapy for patients without suitably matched donors in Vietnam. Infection after transplantation remains a challenge and requires effective management.

Project description:In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Among the 264 patients, 180 (68%) received a BM graft and 84 (32%) received a PB graft. The median patient age was 50 years in both groups. The majority (n = 199; 75%) received reduced-intensity conditioning. The rate of acute leukemia or myelodysplastic syndrome was higher in the BM graft recipients compared with the PB graft recipients (85% [n = 152] versus 55% [n = 46]; P < .01). The median times to neutrophil and platelet engraftment and the incidence of grade II-IV and grade III-IV acute GVHD (aGVHD) were comparable in the 2 groups. Among the patients with grade II-IV aGVHD, the rate of steroid-refractory aGVHD was 9% (95% confidence interval [CI], 5% to 18%) in the BM group versus 32% (95% CI, 19% to 54%) in the PB group (hazard ratio [HR], 3.7, 95% CI, 1.5 to 9.3; P = .006). At 1 year post-HCT, the rate of chronic GVHD (cGVHD) was 8% (95% CI, 4% to 13%) in the BM group versus 22% (95% CI, 14% to 36%) in the PB group (HR, 3.0; 95% CI, 1.4-6.6; P = .005), and the rate of systemic therapy-requiring cGVHD was 2.5% (95% CI, 1% to 7%) versus 14% (95% CI, 7% to 27%), respectively (HR, 5.6; 95% CI, 1.7 to 18; P = .004). The PB group had a significantly higher risk of bacterial and viral infections, with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, nonrelapse mortality, or survival. Our data suggest a benefit of the use of BM grafts over PB grafts for haplo-HCT.

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New-onset post-transplant diabetes mellitus after haploidentical hematopoietic cell transplant with post-transplant cyclophosphamide.

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