Comparison of Outcomes After Human Leukocyte Antigen-Matched and Haploidentical Hematopoietic Stem-Cell Transplantation for Multiple Myeloma
Allogeneic stem-cell transplantation (allo-SCT) remains a critical immunotherapeutic approach for multiple myeloma (MM), leveraging the graft-versus-myeloma effect to achieve durable remission. Despite advancements in autologous SCT and novel therapies, allo-SCT continues to play a role in high-risk or relapsed/refractory MM. Historically, allo-SCT was associated with high treatment-related mortality (TRM), but improvements in conditioning regimens, donor selection, and supportive care have reduced complications. Haploidentical SCT (haplo-SCT) has emerged as a viable alternative for patients lacking matched related donors (MRDs), yet its efficacy and safety in MM remain understudied. This multicenter retrospective study compared outcomes between haplo-SCT and MRD transplantation in MM, addressing gaps in existing literature.
Study Design and Patient Characteristics
The analysis included 97 patients with MM or plasma cell leukemia (PCL) who underwent myeloablative allo-SCT across 13 Chinese centers between 2001 and 2017. Patients were divided into two groups: 70 received MRD transplants, and 27 underwent haplo-SCT. A matched-pair design ensured comparability, with haplo-SCT recipients paired with MRD counterparts based on transplantation year (±2 years), disease status at transplant, and follow-up duration.
Baseline characteristics were balanced between groups. The median age was 45 years (range: 25–63), with 66% male patients. Most (95.9%) had MM, while 4.1% had PCL. High-risk cytogenetic abnormalities, including del17p, t(4;14), or t(14;16), were present in 20.6% of patients. Disease status at transplantation varied: 27.8% were in complete remission (CR), 25.8% in very good partial response (VGPR), 24.7% in partial response (PR), and 15.5% had stable disease (SD), progressive disease (PD), or relapse. Notably, the haplo-SCT group had a higher proportion of patients with suboptimal responses (SD/PD/relapse) at transplantation (37% vs. 15.7% in MRD, P = 0.009).
Transplant Protocols and Supportive Care
Myeloablative conditioning regimens predominated, with busulfan-cyclophosphamide (Bu-Cy) used in 63.9% of cases. Total body irradiation (TBI) was incorporated in 12.4% of transplants, more frequently in haplo-SCT (25.9% vs. 7.1%, P = 0.006). Peripheral blood stem cells (PBSCs) were the primary graft source (57.7%), while combined bone marrow and PBSCs were used in 38.1%. The median infused mononuclear cell (MNC) dose was higher in haplo-SCT (8.49 × 10⁸/kg vs. 7.44 × 10⁸/kg, P = 0.012), though CD34+ cell doses were comparable. Graft-versus-host disease (GVHD) prophylaxis predominantly involved cyclosporine A (CsA)-based regimens (92.8%).
Engraftment and GVHD Outcomes
Neutrophil recovery (≥0.5 × 10⁹/L) by day 21 was similar between groups (94.3% MRD vs. 92.3% haplo-SCT, P = 0.052). Platelet recovery (≥20 × 10⁹/L) by day 60 was marginally lower in haplo-SCT (92.3% vs. 97.0%, P = 0.030). Acute GVHD (aGVHD) incidence did not differ significantly: grades 2–4 aGVHD occurred in 29.2% (MRD) vs. 23.0% (haplo-SCT), and grades 3–4 aGVHD in 7.1% vs. 3.7%. Chronic GVHD (cGVHD), however, was more frequent in haplo-SCT (77.9% vs. 28.4% at 3 years, P = 0.045).
Survival and Relapse Outcomes
Non-relapse mortality (NRM) rates at 1 and 3 years were comparable: 20.5% and 24.2% for MRD vs. 16.8% and 28.7% for haplo-SCT (P = 0.861). Relapse incidence remained high in both groups, with 3-year cumulative rates of 44.4% (MRD) and 57.6% (haplo-SCT) (P = 0.352). Progression-free survival (PFS) and overall survival (OS) did not significantly differ between donor types. The 3-year PFS was 45.4% for MRD vs. 26.8% for haplo-SCT (P = 0.670), while 3-year OS was 60.1% vs. 37.5% (P = 0.223). Suboptimal disease status (less than PR) at transplantation independently predicted higher relapse risk (HR = 2.483, P = 0.009) and inferior PFS (HR = 1.939, P = 0.02).
Multivariate Analysis and Risk Factors
Multivariate models confirmed no significant differences between haplo-SCT and MRD in NRM, relapse, PFS, or OS. High-risk cytogenetics did not adversely affect outcomes, suggesting allo-SCT may mitigate their prognostic impact. Transplantation after 2010 correlated with reduced NRM (HR = 0.296, P = 0.003), reflecting advances in supportive care. Chronic GVHD did not translate into superior disease control despite its higher incidence in haplo-SCT.
Clinical Implications and Limitations
This study demonstrates that haplo-SCT achieves outcomes comparable to MRD transplantation in MM, expanding donor options for patients without matched siblings. The comparable NRM and relapse rates challenge historical concerns about haplo-SCT toxicity, underscoring its feasibility with modern protocols. However, high relapse rates persist, emphasizing the need for post-transplant strategies like maintenance therapy or minimal residual disease (MRD)-guided interventions.
Limitations include the retrospective design, small haplo-SCT cohort, and heterogeneity in conditioning regimens. The predominance of Bu-Cy and variable use of TBI may limit generalizability. Additionally, cytogenetic data were incomplete, and maintenance therapy details were unavailable, potentially confounding survival outcomes.
Conclusion
Haploidentical SCT is a safe and effective alternative for MM patients lacking HLA-matched donors, with engraftment, GVHD, and survival outcomes comparable to MRD transplantation. Disease status at transplantation critically influences prognosis, highlighting the importance of optimal disease control before allo-SCT. Future studies should explore post-transplant maintenance therapies and larger cohorts to validate these findings.
doi.org/10.1097/CM9.0000000000000341
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