Haploidentical Donors/Posttransplant Cyclophosphamide Produces Outcomes Similar to Matched Unrelated Donor Transplantation in Myelofibrosis

Haploidentical donors and posttransplant cyclophosphamide is a comparable alternative to matched unrelated donors for patients with myelofibrosis receiving blood or marrow transplant without matched sibling donors, although matched sibling donors, when available, remain the preferred donor option.

Tania Jain, MD

Tania Jain, MD

Haploidentical donors (HD) and posttransplant cyclophosphamide (PTCy) is a comparable alternative to matched unrelated donors (MUD) for patients with myelofibrosis receiving blood or marrow transplant (BMT) without matched sibling donors, although matched sibling donors, when available, remain the preferred donor option, according to findings from a study presented at the 2023 Transplantation and Cellular Therapy Meeting.

In the presentation, Tania Jain, MD, of Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, discussed data from the study, which aimed to compare the outcomes with 4 common donor types when using HD and PTCy (HD-PTCy).

Previously, registry data that came out prior to the emergence of HD have shown the superiority of MSD compared with MUD donors in treating patients with myelofibrosis. With BMT using HD-PTCy in myelofibrosis, a multicenter study then led to an overall survival (OS) rate of 72% in patients and a disease-free survival (DFS) of 44% at 3 years.

To further evaluate the unknown outcomes of the 4 donor types, HD-PTCy, MSD, MUD, and mismatched unrelated donor (MMUD), experts reviewed data from CIBMTR, which is a working group of over 500 BMT centers. Investigators obtained data from 1057 adult patients who underwent a first BMT using peripheral blood graft between 2013-2019 for chronic phase myelofibrosis (<10% blasts) using HD-PTCy, MSD, MUD and MMUD.

Across the 4 donor groups, standard univariate and multivariate analyses were conducted for comparison. In the multivariate analysis, control variables included age, gender, race and ethnicity, sub-diagnosis, time from diagnosis to BMT, dynamic international prognostic scoring system (DIPSS) at BMT, prior use of JAK inhibitors, splenomegaly at BMT, donor-recipient sex match and CMV status, conditioning intensity, and year of BMT.

"Based on this real-world, retrospective study, over the years, haplo donors have offered a viable and comparable transplant option with the emergence of PTCy in non-White, non-Caucasian patients, who are commonly underrepresented in the registry," Jain said during the presentation.

In the study, HD was defined as a family donor mismatched by 2 or more HLA loci, MUD was defined as matched at allele level HLA-A, -B, -C, and -DRB1, and MMUD as unrelated and mismatched by 2 or more HLA loci.

The study excluded patients who underwent BMT using cord blood graft or T-cell depletion.

Among the 1057 patients enrolled, 121 were HD, 312 were MSD, 547 were MUD, and 68 were MMUD. Across donor types of HD vs MSD vs MUD vs MMUD, a majority of patients were male (60% vs 59% vs 57% vs 59%), White (60% vs 80% vs 90% vs 76%) and had a sub-diagnosis of primary myelofibrosis (70% vs 67% vs 69% vs 72%).

Baseline characteristics showed that the median age for HD to be 63 years (range, 34-75), 61 (range, 34-75) for MSD, 63 (range, 32-78) for MUD, and 60 (range, 38-72) for MMUD. The median time from diagnosis to BMT was 34 months (2-401), 28 months (2-417), 29 months (2-522), and 31 months (4-363) for HD, MSD, MUD, and MMUD, respectively. Across all donor groups, 26%, 47%, 44%, and 46% received myeloablative conditioning while 72%, 50%, 55%, and 53% received non-myeloablative conditioning in the HD, MSD, MUD, and MMUD groups, respectively.

The median follow-up in the HD group was 36 months (range, 9-77), 46 months (range 13-100) for MSD, 48 months (range, 4-98) for MUD, and 49 months (range, 23-98) for the MMUD donor type.

Univariate 3-year estimate for OS was 58% for HD (49%-57%), 68.3% for MSD (63%-74%), 61.5% for MUD (57%-66%), and 57.9% for MMUD (46%-70%) for a P value of .044. At 1-year, primary graft failure was at 19% for HD, 4% for MSD, 8% for MUD, and 6% for MMUD (P < .001).

For DFS, rates were 28%, 31%, 27%, and 29% (P = .21), relapse was 44%, 52%, 48%, and 44% (P = .68), and non-relapse mortality (NRM) was 27%, 17%, 25%, and 28% (P = .03), for HD, MSD, MUD, and MMUD, respectively.

Rates of grade 3-4 acute graft vs host (GVHD) disease at 3 years were 16% for HD, 24% for MSD, 18% for MUD, and 28% for MMUD (P = .05). Chronic GVHD rates at 3 years were 42%, 57%, 52%, and 50%, respectively (P = .07).

"We need to work toward better disease control prior to transplant or maintenance strategies after transplant to improve [relapse rates]," Jain explained.

In the multivariate analysis, the OS at 3 months or less from BMT was superior with MSD vs HD-PTCy (HR, 0.22; 95% CI, 0.11-0.46; P < .0001) compared with MSD (HR, 0.30; 95% CI, 0.17-0.53; P < .0001) vs MMUD (HR, 0.28; 95% CI, 0.09-0.93; P = .04). This was largely attributed to lower NRM with the use of MSD.

After the first 3 months, the OS did not significantly differ between HD-PTCy, MUD, or MMUD. After 3 months post BMT, NRM, relapse, or DFS, there was also no statistically significant difference between the 4 donor types.

Looking at NRM in the multivariate analysis, the rate was superior with MSD vs MUD (HR, 0.69; 95% CI, 0.50-0.94; P = .02), and vs MMUD (HR, 0.28; 95% CI, 0.09-0.93; P = .04). Rates were also superior compared with MUD vs MMUD (HR, 0.94; 95% CI, 0.38-2.31; P = .89).

Though MSD is the preferred donor in patients with myelofibrosis, HD-PTCy has shown to be a similar option to unrelated donors for BMT for patients who lack MSD. Overall, these data highlight the need to reduce early NRM and long-term relapse rates in this diagnosis, concluded Jain.


Jain T, Estrada-Merly N, Salas MQ, et al. Posttransplant cyclophosphamide-based transplantation from haploidentical donors has similar outcomes as unrelated donor transplantation in myelofibrosis: A center for international BMT research (CIBMTR) study. 2023 Transplantation and Cellular Therapies Meeting. February 15-19, 2023. Orlando FL. Abstract 10.

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