Pre-Transplant Diabetes Is Associated with Increased Risk of Relapse after HCT: A Single Center Experience

Background: Evaluating nutritional status at allogeneic hematopoietic cell transplantation (HCT) is of outmost importance. Moreover, obesity and diabetes mellitus (DM) can modulate immune response, which may impact HCT outcomes.

Methods: We retrospectively analyzed 158 patients who underwent HCT in a single center between January 2020 and June 2023. Nutritional status was assessed by Nutritional Risk Index (NRI) and Patient-Generated Subjective Global Assessment (PG-SGA). BMI (usual, pre-HCT and at discharge), previous diagnosis of DM and biochemical parameters were additionally collected.

Results: Median age was 57 (range 20-74) years old and 54% of patients were male. Diagnosis was acute myeloid leukemia in 40% and lymphoproliferative disease in 30%; disease risk index was intermediate in 50% of the cases. Disease status at HCT was complete remission in 75%. Median follow up was 31 (range 11-52) months. Fifty-one (32%) had a HCT comorbidity index of 0 and Karnofsky performance status was 100% in 48% of the patients. Forty-six patients (29%) had received 3 or more lines of therapy before HCT including autologous stem cell transplant in 27 (17%). Graft source was peripheral blood stem cells in 93% of the cases. Donor type was haploidentical in 39%, HLA identical sibling in 22%, matched unrelated in 35% and mismatched unrelated in 4% of the cases. Most of the patients (n=132, 84%) underwent a reduced intensity conditioning (RIC) regimen; the most frequent chemotherapy regimen was thiotepa, busulfan and fludarabine RIC (n=92). Graft-versus- host disease (GvHD) prophylaxis consisted of tacrolimus and mycophenolate mofetil in 69% of the patients. One hundred twenty-two (77%) patients received PTCY. PG-SGA was scored as A (well nourished) in 52% (n=82), B (moderately malnourished) in 44% (n=70) and C (severely malnourished) in 4% (n=6) of the patients. NRI was mild in 14 (9%), moderate in 33 (21%) and severe in 4 (3%) patients. The median serum albumin was 41.5 (range 27-55) g/L and 18 (11%) patients had pre-HCT DM. Notably, all patients with DM were in the overweight (n=8, 44%) or obese BMI category (first class obesity n=5; second class obesity n=3, third class obesity n=2). Oral nutritional support (ONS) before HCT was used in 43% of the patients while 86% needed ONS during HCT hospitalization. Total parenteral nutrition was used in 36% of patients with a median of 12 (range 4-60) days. Median usual BMI before HCT, at HCT and at discharge were 25.8 (17.1-45.2), 25.8 (18.7-45.1) and 24.8 (17.6-43.7), respectively. According to BMI at HCT, 56 (35%) were in the overweight category, 27 (17%) in first class obesity, 7 (4%) in second class obesity and 5 (3%) in third class obesity. A healthy weight was detected in 40% of the patients and none of them was underweight. Only one patient was underweighted 3 months before HCT recovering in the health category at HCT.

The cumulative incidence of grade II-IV acute GvHD was 20% (95% CI 14-27%) at 100 days. At 30 months, the cumulative incidence of chronic GvHD was 17% (95% CI 12-24%). Non-relapse mortality (NRM) and relapse incidence (RI) were 25% (95% CI 19-33%) and 24% (95% CI 18-32%) at 30 months, respectively. Overall survival (OS) and progression free survival (PFS) were 57% (95% CI 49-64%) and 50% (95% CI 42-58%), respectively. Sixty-four patients died. Cause of death was relapse in 15 (23%), infection in 29 (45%), GvHD in 4 (6%), multi organ failure in 12 (18%) and other causes in 4 (6%).

In univariate analysis, no statistically significant difference in neutrophil engraftment, OS, PFS, NRM, GvHD was identified according to nutritional scores or DM. Conversely, RI was higher in patients with DM (46% versus 21%, p=0.03). This finding was confirmed on multivariate analysis adjusted for age, conditioning intensity, DM, gender and NRI. DM was associated with higher RI (HR 2.24, 95%CI 0.99-4.9; p=0.04). No statistically significant differences were found with respect to NRM, PFS, OS and acute and chronic GvHD.

Conclusion: In our study, we observed a higher RI in patents with DM. Pre-existing DM and obesity may influence outcomes of HCT. Larger prospective studies could further evaluate whether a better glycemic control before HCT or during HCT complications, such as GvHD, can improve survival rates.

Mussetti:Gilead: Research Funding; SANOFI: Other: speaking and teaching; JAZZ PHARMA: Other: speaking and teaching; Atara, Takeda: Other: Participation in clinical trials (PI); Takeda, BMS , Gilead, Sanofi: Other: Honoraria for lectures; Merck, Jazz Pharma: Other: Honoraria for advisory board activities. Gonzalez Barca:Takeda: Speakers Bureau; Lilly: Consultancy; Gilead: Consultancy; Incyte: Consultancy, Speakers Bureau; Abbvie: Consultancy, Other: Travel funding, Speakers Bureau; Janssen: Consultancy, Other: Travel funding, Speakers Bureau; Roche: Speakers Bureau; Kiowa: Consultancy, Speakers Bureau; Novartis: Consultancy; AstraZeneca: Speakers Bureau; Beigene: Consultancy; EUSAPharma: Consultancy, Other: Travel funding, Speakers Bureau. Sureda Balari:BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding, Speakers Bureau; GETH-TC: Other: President; Alexion: Honoraria; Roche: Honoraria, Other: Travel Expenses; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; EBMT: Other: President; Takeda Pharmaceutical: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; Mundipharma: Consultancy; Bluebird: Membership on an entity's Board of Directors or advisory committees.