Outcomes in Underweight Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Introduction:

Weight loss and cachexia is a hallmark of cancer. The role of body mass index (BMI-kg/m2) is still controversial in allogeneic hematopoietic stem cell transplant (allo-HSCT) patients. Low BMI is a potential cause of inferior outcomes in allo-HSCT; however, data regarding the impact of being underweight on transplant outcomes is limited. We investigated the impact of low body mass index (BMI) of less than 18.5 kg/m2 on outcomes after allo-HSCT.

Methods:

This retrospective multicenter study included allo-HSCT recipients in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry data from 2013 to 2018 (P5646, Ramathan et al.). Chi-square and t-tests were used to compare categorical and continuous baseline demographics. Univariate and multivariate Cox regression analyses were performed to investigate the post-transplant outcomes in underweight recipients, such as overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD), and chronic graft-versus-host disease (cGVHD), and engraftment. The multivariate analyses were adjusted for significant variables identified in the univariate analysis. The hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Statistical analyses were conducted using SPSS version 28 and R version 4.16. Statistical significance was defined as p <0.05.

Results:

We included 7545 allo-HSCT recipients. Of these, 1254 (16.6%) were underweight (BMI <18.5 kg/m2), and 6291 (83.4%) patients had a BMI of 18.5 mg/m2 or higher. The median age at the time of transplant was 56 years; 58% of the patients were men. Ethnicities were Caucasian (76%), Hispanic (8%), African American (6%), Asian (5%), and others/not available (5%). The primary disorders included acute myeloid leukemia (47%), myelodysplastic syndromes (34%), and acute lymphoblastic leukemia (18%). Myeloablative conditioning was used in 53% of patients. Donor types were matched unrelated (49.5%), matched related (34%), and cord blood (16%). Graft sources were peripheral blood stem cells (68%), umbilical cord blood (16%), and bone marrow (15%). GVHD prophylaxis regimens included tacrolimus or cyclosporine-based (87%), post-transplant cyclophosphamide-based (9%), CD34 selection (2%), and others (1.7%). Univariate regression analyses revealed that underweight recipients had improved outcomes with a superior OS (HR 0.85, 95%CI 0.77-0.93, p<0.001), lower NRM (OR 0.19, 95%CI 0.16-0.22, p<0.001), lower rates of chronic GVHD, (HR 0.89, 95% CI 0.81-0.98, p=0.02), faster neutrophil engraftment (HR 0.82, 95%CI 0.77-0.88, p<.001) and faster plateletengraftment (HR 0.82, 95%CI 0.77-0.87, p<0.001). Underweight status did not impact DFS, relapse, and incidence of acute GVHD. In the multivariate analysis adjusted for significant factors identified in the univariate analyses, including age, gender, graft type, performance status, and GVHD prophylaxis, being underweight did not remain a significant predictor of any of the post-transplant outcomes.

Conclusion:

Our study found that post-transplant outcomes are at least comparable in underweight versus other allogeneic hematopoietic stem cell transplant recipients. A low body mass index with a good performance status should not preclude allo-HSCT in acute leukemia and myelodysplastic syndrome patients.

Ahmed:Kite, a Gilead Company: Research Funding; Bristol Myers Squibb: Consultancy. Hamadani:Genmab: Consultancy; Omeros: Consultancy; Kite Pharma: Consultancy, Speakers Bureau; Astellas Pharma: Research Funding; BMS: Consultancy; Caribou: Consultancy; Allovir: Consultancy; CRISPR: Consultancy; Autolus: Consultancy; Forte Biosciences: Consultancy; AbbVie: Consultancy; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau; Spectrum Pharmaceuticals: Research Funding; Sanofi Genzyme: Speakers Bureau; BeiGene: Speakers Bureau; AstraZeneca: Speakers Bureau; Byondis: Consultancy; CRISPR: Speakers Bureau; DMC, Inc: Speakers Bureau; Genentech: Speakers Bureau; Myeloid Therapeutics: Speakers Bureau; Takeda: Research Funding. McGuirk:Autolus: Consultancy; BMS: Consultancy; Novartis: Consultancy; Kite: Consultancy; Allo Vir: Consultancy; Envision: Consultancy; CRISPR therapeutics: Consultancy; NEKTAR therapeutics: Consultancy; Caribou bio: Consultancy; Sana technologies: Consultancy; Legend biotech: Consultancy. Mushtaq:Iovance Biotherapeutics: Research Funding.