Transplant Outcomes in Older Patients Are Comparable to Outcomes in Younger Patients after Hopkins' Non-Myeloablative Flu Cy TBI + PT-Cy Regimen

Introduction:  Hematologic malignancies are largely diseases of older age.  Advances in graft versus host disease (GVHD) prophylaxis utilizing post-transplant cyclophosphamide (PTCy) expanded the use of haploidentical hematopoietic cell transplantation and has encouraging results in non-haploidentical hematopoietic cell transplantation as well.  The Hopkins' regimen using fludarabine, cyclophosphamide, total body irradiation and post-transplant cyclophosphamide (FluCyTBI-PTCy) has been associated with low toxicity, and low rates of acute and chronic GVHD. Limited data exist comparing the toxicity of this regimen in older versus younger patients. We hypothesized this regimen would be well tolerated in older patients.

Methods: We performed retrospective analysis of patients who underwent allogeneic hematopoietic cell transplantation utilizing FluCyTBI-PTCy regimen between 2009 and 2014 at our institution. Patients were eligible regardless of donor type or source.  Patients were divided on the basis of age (≥50 vs <50) and their transplant outcomes assessed. Kaplan-Meier models were used to estimate overall, disease free and event free survival. Cumulative incidence was estimated using the method of Klein and Moeschberger.

Results:  A total of 46 patients were identified, 23 patients were < 50 years of age at the time of their transplant.  Diagnoses included AML (61%), ALL (13%), AA (4%), NHL (9%), MDS (7%), CML (4%), and CLL (2%).  Age at transplant was 19– 73 years, with a median of 49.  Donor sources included: unrelated (15%), haploidentical (83%) and matched sibling (2%).  At transplant, active disease was present in 3 / 6 ALL patients, 11 / 28 AML patients, 3 / 4 NHL patients and 1 / 2 CML patients. Median overall survival (OS) was 17.9 months.  There was no evidence of a difference in OS by age category (p = 0.74) (Figure 1).  Non-relapse mortality (NRM) at 6.5 months was 16.1% in the overall population and 20.7% in older patients.  There were no differences in NRM by age category (p = 0.90).  Also, no differences were seen in the median DFS or EFS by age group (data not shown).  Overall cumulative incidence of relapse at 6 months was 26.9%.  Cumulative incidence of relapse in younger patients was 35.7% and 18.3% in older patients (p = 0.76).   Similarly there was no statistically significant difference in the acute or chronic GVHD rates in the two cohorts (data not shown).

Conclusions:  There is limited data on outcomes of Hopkin's non-myeloablative FluCyTBI-PTCY transplant regimen in older patients. Here we demonstrate outcomes in older patients that are comparable to those in younger patients. Though limited by the small number of patients our results suggest this regimen is safe with low NRM, and favorable OS. The regimen provides a potentially curative option for older patients without excess toxicity.

Figure 1.