Feasibility of Hematopoietic Stem Cell Transplantation for T-Prolymphocytic Leukemia. Experience of a Large Referral Center

Background: T-cell prolymphocytic leukemia (T-PLL) is a rare neoplasm with an aggressive course and a median survival of < 1 year. Outcomes have improved since the advent of alemtuzumab but the duration of response remains short. Hematopoietic stem cell transplantation (HSCT) is thought to offer long term disease control; however the feasibility of this approach is not well defined.

Aims: To determine the transplant referral pattern and outcomes from a large center and to ascertain the survival of patients (pts) treated with alemtuzumab based regimens.    

Methods: Following IRB approval, all pts diagnosed with T-PLL from 1997-2014 at Mayo Clinic Rochester were identified.  T-PLL diagnosis was established based on the 2008 WHO criteria. Survival was estimated using the Kaplan-Meier method with log ranks to compare curves.

Results: 41 pts with T-PLL were identified; 23 (56%) were males, with a median age at diagnosis of 66 years (range, 32-85). Median follow up was 18 months (0.4-66.1). At last follow up, 32 pts (78%) have died. Lymphadenopathy was present in 68%, hepato-splenomegaly in 61% and cutaneous infiltration in 10%. Median HB was 13.5 gm/dl (6.6-17.3), WBC 26.25 x 10⁹/L (9.4-551), ALC 17.1 x 10⁹/L (5.7-540) and Plt 164 x 10⁹/L (5-299). Among evaluable pts, FISH analysis was positive for 14q32 in 27/28, trisomy 8 in 4/10, 11q22 deletion in 4/6 and 17p deletion in 2/3. Next generation sequencing in two pts revealed ATM R3008H with JAK3 M511I mutations in one and ATM loss in the other. Twenty (49%) pts received alemtuzumab based therapy, 13 as intravenous, 4 as subcutaneous injection and 3 unknown. Fourteen (34%) received non-alemtuzumab based therapies, 2 pts received best supportive care, while 4 (10%) have not required treatment to date. Median survival for pts receiving alemtuzumab based therapy was 29.5 vs 10.3 months for all other therapies (P 0.0011). Median survival between intravenous vs subcutaneous alemtuzumab administration was 40.5 vs 10.9 months (P 0.0011). Thirteen pts were > 70 years of age and not considered for HSCT. Among the eligible cohort, 22 (85%) were unable to proceed due to progressive disease (20), lack of donor (1) or failed autologous mobilization (1). Only 15% of the eligible pts received HSCT; 3 underwent myeloablative allogeneic HSCT, while one patient underwent an autologous HSCT. Median survival post-transplant was 4 months (2.5-32). All three allogeneic recipients died from graft versus host disease while the autologous recipient died within 4 months post-transplant from disease progression.

Conclusion: Alemtuzumab based regimens are associated with improved survival outcome in pts with T-PLL. Although transplant is thought to be the best consolidation approach, a striking minority were eligible for such therapy mainly due to progressive disease. Recurring JAK3 mutations and ATM deletions reported by us and others should be exploited for future clinical trials.