Matched Cohort Analysis of Allogeneic Hematopoietic Cell Transplantation (HCT) with Total Marrow Irradiation/Fludarabine/Melphalan (TFM) Versus Fludarabine/Melphalan (FM) Conditioning for Acute Leukemia

We analyzed 72 patients with acute leukemia or MDS who received either FM (N=36) or TFM (N=36) HCT. Eligibility criteria for TFM were age > 50 years of age or compromised organ function (COF); high-risk remission or marrow blasts ≤10%. TFM patients were matched to a set of FM patients based on age, gender, diagnosis and disease risk (low, intermediate, high). All patients received FM with fludarabine 25 mg/m²/d × 5 days and melphalan140 mg/m²/d × 1 day, and TMI was delivered at 150cGy/fraction in 8 fractions over 4 days in the TFM group. Supportive care and treatment for prevention of GVHD were given according to our institution standard guidelines for both groups.

Demographic characteristics were similar, including gender (20 females, 55.6%) and age (median 58 years, range: 22–68 in TFM and 20–68 in FM). The proportions of patients by diagnoses were similar: AML (n=27), ALL (n=7), MDS (n=2). Disease risk assignments in both groups were: Low risk (n=15), intermediate (n=6), high (n=15). There were 15 and 13 pts with active disease in FM and TFM, respectively. HLA-identical siblings (n=16, 44.4%) or matched unrelated donor (n=20, 55.6%) were used in each group. Outcomes are reported for the TFM and FM recipients, respectively as follows: myeloid recovery was documented on day 13.5 (9–24) and 15 (8–20). Transplant-related toxicities were limited to grade 3 or less in both groups. The most common grade 3 toxicities were: mucositis, n=9 and n=7 and bacterial infection, n=10 and n=11, respectively. Acute GvHD grade II-IV occurred in 20 pts (55%) and 19 (53%). Extensive chronic GVHD was documented in 24 (67%) and 20 (56%) pts. Twenty-one and 18 patients are alive at a median of 30.2 months and 35.3 months in the TFM and FM, respectively. The relapse cumulative incidence at 2 years post HCT was 11.1% (TFM) compared to 30.6% (FM) (p=0.06) (insert ). With a median follow-up of 31.7 months (4.1 – 62.5) for alive patients, the 2-year overall and progression-free survival estimates are 57.2 % (95% CI, 46.6–66.4) -TFM, and 62.8% (95% CI, 51.8–72.0) -FM, and 57.7% (95% CI, 47.2–67.0) -TFM, and 48.5% (95% CI, 40.2–56.3) -FM, respectively.

The addition of TMI at a dose of 1200 cGy to FM is safe and tolerable and may decrease the risk of relapse related mortality.

No relevant conflicts of interest to declare.