Impacts of Comorbidities on Outcomes of Patients (pts) Diagnosed with B-Cell Malignancies and Treated with Allogeneic Hematopoietic Cell Transplantation (HCT) Using Nonmyeloablative (NM) vs Myeloablative (M) Conditioning.
Authors: Sorror Mohamed , Sandmaier Brenda M. , Storer Barry , Maris Michael B. , Maloney David G. , Storb Rainer 
Published: October 2019

We developed a new HCT-specific comorbidity index (HCT-CI) as a sensitive tool to capture pretransplant comorbidities among pts given allogeneic HCT (Sorror et al. Blood.2005; 106, 2912–2919). Here, we retrospectively analyzed whether the HCT-CI was useful in assessing how pts with B cell malignancies tolerated NM vs M-HCT. Results among consecutive pts (n=125) given NM-conditioning with 2Gy total body irradiation (TBI) (19%) or 2 Gy TBI combined with 90 mg/kg of fludarabine (81%) were compared to those among concurrent M-pts (n=55) conditioned with cyclophosphamide plus busulfan (15%) or 12Gy TBI (85%). Diagnoses were non-Hodgkin lymphoma (NHL, 80% vs 52%), Hodgkin disease (HD, 5% vs 20%), and chronic lymphocytic leukemia (CLL, 15% vs 28%), respectively. At HCT, NM-pts differed substantially from M-pts with respect to age (median 52 vs 40 years,), prior treatment regimens (median 5 vs 3), prior failed high-dose HCT (45% vs 9%), unrelated donors (43% vs 18%), and G-PBMC as stem cell source (99% vs 78%). Smaller differences existed for disease chemo-sensitivity (58% vs 69%) and aggressive disease (56% vs 64%). HCT-CI scores >0 were found among 70% and 58% of NM and M-pts, respectively. After HCT, 2-year NRM and survival were 26% and 59% vs 29% and 51% among NM and M-pts, respectively. There were no statistically significant differences in NRM (19% vs 4%, p=0.3) and survival (70% vs 70%, p=0.7) between NM and M-pts with HCT-CI scores of 0; however, this comparison was limited by the small numbers of non-relapse deaths. NM-pts with HCT-CI scores of ≥ 1 had statistically significantly lower NRM (29% vs 47%, HR=0.50, p=0.03, Figure) and better survival (54% vs 37%, HR=0.60 p=0.05) compared to M-pts. These differences remained after adjusting for pretransplant differences (NRM, HR=0.3, p=0.006; survival, HR=0.33, p=0.002). In a further analysis which included all pts, increasing HCT-CI scores and M-conditioning were important risk factors for NRM and survival (Table). We concluded that pts with B cell malignancies and HCT-CI scores of ≥1 tolerated NM-HCT better than M-HCT, and prospective randomized trials may be warranted to confirm this result. Additional data are needed to clarify possible differences between M and NM-conditioning for patients without comorbidities.

Table: Multivariate risk factors for HCT outcomes NRM Survival HR p HR p *Lower HR means better survival. Other risk factors, including donor type; CMV sero-status; and disease chemo-sensitivity, were not significant. Conditioning NM 1.0 1.0 M 3.03 0.007 2.27 0.006 HCT-CI scores 0 1.0 1.0 1–2 2.56 1.78 ≥3 3.85 0.001 2.44 0.005 Diagnoses NHL 1.0 1.0 HD 0.79 0.98 CLL 0.55 0.3 0.46 0.03 Graft G-PBMC 1.0 1.0 Marrow 0.23 0.03 0.38 0.03 Age, years <50 1.0 1.0 ≥50 2.72 0.01 1.53 0.14 Prior regimens 1–2 1.0 1.0 3–5 2.02 1.71 ≥6 0.79 0.02 1.44 0.24 Figure: 2 year NRM among pts with HCT-CI scores of ≥1 Figure:. 2 year NRM among pts with HCT-CI scores of ≥1