LY-02. Upfront allogeneic HSCT in a patient with plasmablastic lymphoma with TP53 mutation
Nelly G. Gabeeva, Daria A. Koroleva, Mikhail Yu. Drokov, Bella V. Biderman, Svetlana A. Tatarnikova, Alla M. Kovrigina, Tatiana N. Obukhova, Larisa A. Kuzmina, Evgeny E. Zvonkov, Elena N. Parovichnikova
National Medical Research Center of Hematology, Moscow, Russia
Correspondence:
Mikhail Yu. Drokov, e-mail: mdrokov@gmail.com
Summary
Plasmablastic lymphoma (PBL) is a highly aggressive B-cell lymphoma, strongly associated with immunodeficient states. But up to one third of cases are reported to occur in immunocompetent patients (ic-PBL), which indicates the heterogeneity of PBL. In contrast to HIV-related PBL, ic-PBL cases exhibit EBV negativity and some differences in the spectrum of genetic alterations. Limited data has been presented about the use of lenalidomide in PBL. Allo-HSCT represents the most powerful treatment for TP53mut lymphomas, but its role in the treatment of PBL remains uncertain. Herein, we report on our experience with up-front allo-HSCT after high-dose chemotherapy in a patient with ic-PBL with complex karyotype and TP53 abnormality.
Clinical case
A 43 year-old HIV-negative male was presented in October 2020 with the 2 months history of left palatine tonsil enlargement and increasing difficulty in swallowing. PET/CT showed enlarged hypermetabolic left palatine tonsil (30×35×53 mm, SUV 33.27) and jugular lymph nodes (20×18 mm, SUV 30.50). The oropharyngeal lumen at that level was deformed and narrowed to a maximum of 2 mm. Histological and IHC study of tonsil biopsy specimen revealed lymphoid infiltration by large cells with immunophenotype CD45, CD38, CD138, CD79a, EBV-, high expression of с-Myc and MUM1, Ki-67 80%. FISH examination of the tumor biopsy revealed t(8;14)(q24;q32), deletion of BCL2/18q21 and decrease in the intensity of the fluorescent signal from one of the 17p13/TP53 loci. Deletion c. 529_546del (p.Pro 177_Cys182del) in 5 exon TP53 gene was found by NGS. The diagnosis of PBL with BCL2, с-MYC and TP53 aberrations was established. The patient underwent therapy according to the m-NHL-BFM-90 protocol, which included 4 courses of chemotherapy (blocks A) with lenalidomide (25 mg daily for 10 days of each course). In February 2021, he underwent allo-HSCT from a related HLA-haploidentical donor; conditioning regimen (fludarabine 180 mg/m2 + busulfan 8 mg/kg). A total of 6.2×106/kg of CD34+ cells were transfused. Immunosuppressive therapy was carried out according to the schedule with cyclophosphamide 50 mg/kg (d+3 and +4), cyclosporine 3 mg/kg/day, and mycophenolate mofetil 3 g/day from +5 days. Neutrophil and platelet engraftment were achieved on day +20. There were no serious complications in the post-transplant period. Examination a month later revealed 100% donor chimerism. Follow-up PET/CT was performed 3 months after allo-HSCT. The images showed full resolution of size and hypermetabolic activity in palatine tonsil. At 6 months after allo-HSCT, the patient is in complete remission with no signs of GVHD.
Conclusion
Our study has demonstrated that high-dose induction in combination with lenalidomide followed by up-front allo-HSCT is feasible and effective treatment strategy for transplant-eligible patient with PBL. The superiority of this strategy should be determined in prospective studies.
Keywords
Plasmablastic lymphoma, allo-HSCT, upfront, m-NHL-BFM-90, lenalidomide.
