ISSN 1866-8836
Клеточная терапия и трансплантация

MP-04. A clinical case of the donor-derived myelodysplastic syndrome after allogeneic bone marrow transplantation

Olga M. Koroleva, Alina V. Kochno, Luiza A. Karaseva, Natalya A. Petinati, Vera A. Vasilyeva, Marya V. Dovydenko, Zoya V. Konova, Dmitry A. Mokin, Tatyana N. Obukhova, Larisa A. Kuzmina, Elena N. Parovichnikova

National Medical Research Center for Hematology, Moscow, Russia

Contact: Dr. Olga M. Koroleva, phone: +7 (964) 594-37-77, e-mail: koroleva.o@blood.ru

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

Summary

Donor-derived acute leukemia or myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a rare phenomenon, which was first described in 1971. According to the literature, the frequency of donor-derived hematological malignancies/leukemia (DDL) is less than 2% of blood cancers following allo-HSCT. It has been shown that transplantation of donor cells with clonal hematopoiesis (CH) plays a key role in the development of DDL. The incidence of CH rises with age and, according to some data, increases the risk of blood cancer.

Clinical case

A 67-year-old woman was diagnosed with acute lymphoblastic leukemia, variant B-II in November 2017. Remission was achieved after 1st course of induction chemotherapy according to the MOAD protocol. The disease relapse was diagnosed in December 2018 during the chemotherapy. The phenotype of tumor cells corresponded to BI-ALL, chimeric transcripts of BCR/ABL p190, p210 were not detected. In 35% of nuclei were detected 1-2 additional signals from the PDGFRA/4q12 gene locus (polysomy 4? duplication 4q12?), therefore the patient was treated with 3 courses of blinatumomab in combination with dasatinib. MRD negative remission was achieved. Allogeneic bone marrow transplantation from a related HLA-identical 54-years old brother was performed in July 2019. Conditioning regimen consisted of fludarabine, busulfan, ATG. Graft-versus-host disease (GvHD) prophylaxis included of cyclosporine A and low doses of methotrexate. Engraftment occurred at day +21. Due to mixed chimerism immunosuppressive therapy was withdrawn 3 months after allo-HSCT. Chronic GvHD of skin, oral mucosa, esophagus, and cornea developed in December 2019. GvHD resolved with cyclosporine and mycophenolate mofetil, however, keratoconjunctivitis persisted. The patient was in MRD negative ALL remission with 100% donor chimerism for 3 years after allo-HSCT, when isolated thrombocytopenia up to 42×10^9/L was detected for the first time. It was considered a manifestation of herpesvirus infection (skin biopsy showed HHV6 replication). Therapy with valganciclovir was carried out. But in one year pancytopenia was diagnosed: platelets – 39×10^9/L; leukocytes – 2.3×10^9/L, hemoglobin – 103 g/L. Examination confirmed ALL MRD negative remission and 100% donor chimerism. However, cytogenetic analysis detected a male karyotype in 100% of metaphases and clonal changes in 25% of metaphases – trisomy of chromosome 11, (47, XY+11). Blast cells count was 2.4%, and dysplasia was present in more than 10% of cells in 3 hematopoietic lineages in the bone marrow. Mutations in genes associated with MDS – ASXL1, SF3B1, DNMT3A, JAK2 – were not detected. Morphological examination of the bone marrow biopsy showed a hypoplastic variant of myelodysplastic syndrome (MDS). The diagnosis of MDS with multilineage dysplasia, presenting with hypoplasia of hematopoiesis and trisomy 11 from donor hematopoietic cells was established. Intermediate risk group (4 points) according to IPSS-R. Hypomethylation therapy was prescribed for patient, and the opportunity of 2nd allo-HSCT is being discussed. We also checked the condition of donor’s bone marrow. We didn’t find any chromosomal and genetic abnormalities, but histological examination of the BM biopsy revealed moderate hypoplasia of hematopoietic tissue.

Conclusion

In the described case of the MDS development from donor hematopoietic cells, we didn’t find evidence of clonal hematopoiesis in the bone marrow donor, even 4 years after stem cell collection. Presumably, the pathological changes leading to the development of MDS occurred after allo-HSCT and may be associated with disruption of the bone marrow stromal microenvironment, chronic inflammation (viral infection, GvHD), or previous immunosuppressive and cytostatic therapy.

Keywords

Allogeneic bone marrow transplantation, myelodysplastic syndrome, donor-derived.


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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