ISSN 1866-8836
Клеточная терапия и трансплантация

MP-05. Results of allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis

Olga S. Pokrovskaya, Larisa A. Kuzmina, Zoya V. Konova, Vera A. Vasilyeva, Maria V. Dovydenko, Olga M. Koroleva, Anait L. Melikyan, Karen I. Danishyan, Elena N. Parovichnikova

National Medical Research Center for Hematology, Moscow, Russia


Contact: Dr. Olga S. Pokrovskaya, phone: +7 (903) 782-74-95, e-mail: sillywilly@yandex.ru

doi 10.18620/ctt-1866-8836-2023-12-3-1-176

Summary

Allogeneic hematopoietic stem cell transplantation (allo- HSCT) remains the only curative treatment for patients (pts) with myelofibrosis (MF). According to European and American transplant guidelines, allo-HSCT is indicated for intermediate-2 and high-risk MF pts per DIPSS and DIPSS+ criteria. The transplantation decision for intermediate-1 risk group pts is made on a case-by-case basis. The influence of spleen size and the role of splenectomy (SE) prior to transplantation on allo-HSCT outcomes in MF remain contentious. Our study aimed to evaluate the efficacy of allo-HSCT in MF and assess the impacts of spleen size and pre-transplant SE.

Materials and methods

Between 2017 and 2023, 19 allo-HSCT procedures were performed on 15 pts with MF at NMRCH. Second transplants were performed on 4 pts. There were 9 males and 6 females, median age 44 years (range 23 to 63 years). Primary MF was diagnosed in 14 pts, and 1 developed MF secondary to essential thrombocythemia. Disease duration prior to allo-HSCT varied from 4 to 197 months (median 24). As per DIPSS+, 53.4% of pts were classified as high-risk, 26.6% as intermediate-2, and 20% as intermediate-1. Mutations detected included JAK2 V617F in 8 pts, MPL in 2, CALR in 4, and 1 pt was triple negative (ASXL+). SE was performed on 8 pts (53.4%) as preparation for allo-HSCT. Preoperative spleen size varied from 186 to 272 mm (median 246 mm). Time between SE to allo-HSCT was 1 to 6 months (median 3 months). Most pts (86.7%) were treated with ruxolitinib before allo-HSCT, with treatment durations of 3 to 27 months (median 6 months). The first transplant was performed from a fully matched related or unrelated donor in 10 pts, a mismatched unrelated donor (9/10) in 4, and a haploidentical donor in one. Mobilized peripheral blood HSCs served as the HSC source in 66.7% of cases, and bone marrow in 33.3%. All pts received RIC before transplantation. For GvHD prophylaxis, 46.7% of pts received the ATG+CSA+mtx+/-MMF regimen, another 46.7% received PT Cph+CSA+MMF, and in one case, αβT-cell/CD19-depletion was performed.

Results

At a median follow-up of 36 months (range 1 to 46 months), 11 pts (73.3%) are still alive. Engraftment was observed in 11 out of 15 pts. Primary graft failure occurred in 4 pts, with one recovery on day +54 with host hematopoiesis. Poor graft function was noted in two pts. Second transplants were performed in 4 cases (3 due to primary graft failure, one due to increasing mixed chimerism). No disease relapses were recorded. All deaths were due to infections (2 occurred in the context of steroid-refractory acute GVHD grades 3-4, 1 pt died prior to hematopoiesis recovery post-second allo- HSCT, and one due to post-transplant lymphoproliferative disorder). Assessment of post-allo-HSCT chimerism dynamics showed sustained persistence of mixed hematopoiesis. Only 36% of pts demonstrated 95-100% donor hematopoiesis on day +30, 14% had no donor hematopoiesis, and 50% had mixed hematopoiesis, necessitating modification or de-escalation of immunosuppression and donor lymphocyte transfusions. By day +180 post-allo-HSCT, 89% of pts had achieved donor hematopoiesis recovery. We also analyzed the impact of SE on allo-HSCT efficacy. Primary graft failure was noted in 37.5% of pts who underwent SE and in 14.2% of those without SE. Graft hypofunction was observed in one patient from each group. Currently, 87.5% of pts who underwent SE and 57.1% of patients who did not are alive.

Conclusion

In our single-center study, the OS of PMF pts post-allo-HSCT was 72% at a median follow-up of 36 months, with all events occurring within the first year post-allo-HSCT. Extended persistence of mixed chimerism was observed. Accordingly, chimerism and minimal residual disease monitoring is crucial post-transplant. Due to modification and de-escalation of immunosuppression, donor lymphocyte transfusions, most pts achieved donor hematopoiesis recovery by day +180. Despite a limited number of observations, a trend towards improved OS was noted in pts who underwent SE prior to allo-HSCT.

Keywords

Myelofibrosis, allogeneic hematopoietic stem cell transplantation, splenectomy.


Supplement 12-3
09/30/2023

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doi 10.18620/ctt-1866-8836-2023-12-3-1-176

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