In a new study, researchers found clinical utility in detecting human leukocyte antigen (HLA) allele loss in patients with hematologic malignancies experiencing relapse after treatment with haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) and high-dose cyclophosphamide (PTCy). Study results were reported in the journal Frontiers in Immunology.

“Relapse remains the major cause of mortality among patients who undergo Haplo-HSCT,” the researchers explained in their report.

Rescue therapies are available to treat relapse. However, strategies such as the use of donor lymphocyte infusions (DLIs) may produce suboptimal outcomes for patients with HLA loss and could promote graft vs host disease (GVHD), the researchers explained in their report. They suggested that treatments such as chemotherapy, a second transplant, or other therapies are options that may be more appropriate in the setting of HLA loss.

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The study included 181 patients treated at a hospital in Madrid, Spain, with Haplo-HSCT for hematologic malignancies. Genomic DNA was obtained from bone marrow or peripheral blood samples, both at the time of diagnosis and at follow-up after the transplantation procedure, in for evaluations of HLA loss and chimerism.

The 3-year cumulative incidence of relapse in this population was 19.5%, reflecting 37 cases of relapses. A total of 22 cases of relapse were evaluable for HLA loss. In 6 of these patients (27%), there was genomic loss of recipient-specific HLA. The median time to relapse showed a nonsignificant trend of being longer (345 days) for relapses associated with HLA loss than it was for classical relapses (166 days; P =.15). Classical relapses were defined as those without loss of recipient-specific HLA alleles.

For 4 of the 6 patients with relapse and HLA loss, the analysis was retrospective, while 2 patients were assessed prospectively. DLIs and other agents were given to 3 of the retrospectively analyzed patients, and all 3 of these patients reportedly developed severe GVHD. The 4 patients whose relapses were analyzed retrospectively died from disease progression.

The patients with prospectively assessed relapses did not receive DLIs after relapse, and neither developed GVHD after rescue therapy. There was 1 patient who achieved complete remission after receiving brentuximab and a second haplo-HSCT, then later had a second relapse; this patient was being treated with nivolumab at the time of the report. The other patient died from disease progression. This patient had received prophylactic DLIs prior to relapse.

“Based on our results, in the routine management of patients transplanted from Haplo-HSCT or mismatched related donor we carry out chimerism analysis for post-transplantation follow-up,” the study investigators wrote in their report. They suggested that knowledge of HLA status may be useful for guiding rescue treatment.


Muñiz P, Kwon M, Carbonell D, et al. Clinical utility of the detection of the loss of the mismatched HLA in relapsed hematological patients after haploidentical stem cell transplantation with high-dose cyclophosphamide. Front Immunol. 2021;12:642087. doi:10.3389/fimmu.2021.642087