Ex –Vivo T Cell Depleted Allogeneic (TCD) Hematopoietic Stem Cell Transplantation for Advanced Chronic Myelofibrosis: MSKCC Experience

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only potentially curative treatment option for MF.  The role of ex –vivo TCD allo-HSCT hasn’t been reported in patients with advanced MF.

Patients: Between 5/1990-4/2013, 12 pts underwent TCD transplant at MSKCC for MF; 9 had primary MF, 2 post ET and 1 post MDS. Median age was 56 (42.7-65.5). Disease status prior to transplant per DIPSS was: intermediate-1 (4), intermediate-2 (6), and high-risk (2).  Splenectomy prior to transplant was performed in 8 patients.  JAK2 V617F mutation status was known on five patients and was detected on 3.  Five pts received a TCD marrow graft and were conditioned with a TBI-based regimen and 7 pts received TCD peripheral blood graft and were conditioned with a chemotherapy regimen consisting of busulphan, melphalan and fludarabine. All patients received ATG to prevent graft rejection.  Donors were matched related (8) and matched unrelated (4). BM grafts were depleted of T-cells using the soybean agglutinin method followed by sheep RBC rosetting, and PB grafts by immunomagnetic CD34+ selection (Isolex initially and CliniMACS after 09/2011). 

Results:  Three pts died early and were not evaluable for engraftment, the remaining 9 pts engrafted. None of these pts developed acute or chronic GvHD after the primary graft. Of the 9 pts evaluable for long term follow up, 8 are alive with a median follow up time of 12.1 months (3.3-196 months). One pt relapsed 15 months post initial transplant and achieved remission after DLI.  This patient developed acute gut GVHD that responded to steroids. Two additional pts received low dose DLI (0.5x10⁶CD3 cells/kg), one for recurrent viral infections and the other as prophylaxis for relapse. These 2 pts had no GvHD post-DLI.  Out of the 4 pts who did not undergo pre-transplant splenectomy, one required post transplant splenectomy for severe persistent thrombocytopenia which resolved post splenectomy. JAK2 mutation was not detected post transplant in any of the 3 pts.

In this small series of pts, eight out of twelve, 66%, are alive; two of the five pts in the subgroup  cyto-reduced with TBI based regimen and six of the seven patients in the subgroup cyto-reduced with chemotherapy only regimen. The causes of death were: toxicity of the preparative regimen (TBI) in 2, intra-cranial hemorrhage in 1 and unknown in the 4 ^thpatient who died more than 2 years post transplant with no evidence of disease. 

Conclusions:  TCD transplantation can offer long term cure for patients with advanced chronic MF and with no evidence of GvHD in this small cohort of patients.  The early experience at MSKCC with TCD transplant was associated with high rates of early mortality likely related to the high intensity conditioning regimen containing TBI. The current regimen of busulphan, melphalan, fludarabine and ATG has been well tolerated and the majority of pts are alive and disease free.