Haploidentical Transplantation for Advanced Hematologic Malignancies Using Melphalan-Based Conditioning – Mature Results from a Single Center

Haploidentical Transplantation for Advanced Hematologic Malignancies using Melphalan-based Conditioning – Mature Results from a Single Center

Background: Haploidentical stem cell transplantation (HaploSCT) using post-transplant cyclophosphamide (PTCY) has been performed primarily with non-myeloablative conditioning. We are exploring a melphalan-based, myeloablative yet reduced-intensity conditioning (RIC), in an ongoing phase II clinical trial.

Methods: Outcomes of the first 84 pts treated after 01/2009 are reported. 47(56%) pts were males. 74 (88%) pts had their first transplant, 10 (12%) as second transplant. The median age was 46 years (range 19-67). 57 (67.9%) pts were protocol eligible. The conditioning regimen was melphalan 100-140mg/m2 with fludarabine, +/- thiotepa previously described by us (Ciurea SO, BBMT 2012;18:1835). All had a bone marrow graft except 4 pts (95%). Diagnoses were AML/MDS 49 (58.3%), CML 9 (11%), ALL 10 (12%), and lymphoma/CLL 13 (15%) (4 Hodgkin's, 4 NHL, 5 CLL), other 3 (3.6%). 28/46 (61%) pts with myeloid diseases were in CR at transplant, and 15/21 pts with AML in remission had poor-risk cytogenetics. Donors were siblings (N=36), children (N=35), parents (N=12), cousin (N=1).

Results: All pts achieved engraftment except 3 (96.4%), 91.6% with full donor chimerism. Median time to neutrophil engraftment was 18 days (11-43 days). The cumulative incidence of acute and cGVHD for different groups is presented in Table 1. Overall, for the entire cohort, the NRM was 25.7%, relapse rate was 32% and PFS was 42.3%. The median OS for first transplants was 25.6 months (mo) and 6.5 mo for second transplant pts. For pts receiving their first transplant, PFS was similar for those who received full and RIC. Of the 49 pts who had first transplant for AML/MDS, 27 (55.1%) were in complete remission prior to transplant. NRM for these pts was 9%, relapse rate 24.3% and PFS 66.8% at 50 mo of median follow-up (Table 1, Figure 1B).

Conclusions: Melphalan-based conditioning for HaploSCT offers good disease control with low treatment-related mortality. Factors associated with survival were protocol eligibility and remission status for myeloid diseases while the melphalan dose did not impact outcomes. A low relapse rate was observed for lymphoma/CLL pts.

Table 1.

Outcomes overall	All patients (N=84) (%)	Myeloid in CR (N=27) (%)	ALL (N=10) (%)	Lymphoma/CLL (N=14) (%)	P
NRM	25.7	8.9	33.3	25.0	0.17
Relapse Rate	32.0	24.3	25.0	21.4	0.96
PFS	42.3	66.8	41.7	53.6	0.22
aGVHD II-IV	32.6	26.9	50.0	35.7	0.46
aGVHD III-IV	7.8	0	37.5	7.1	0.0038
cGVHD Lim.+Ext.	21.3	21.7	57.1	17.9	0.11
cGVHD Ext. only	10.2	17.7	17.1	0	0.36

Figure 1. A. PFS first transplants, all patients; B. PFS for myeloid patients in remission.