Autologous Stem Cell Transplantation for Myeloma with CKD

Subbaiah RM1, Prabhakaran Shankar2

Consultant Clinical Haematologist, Kauvery hospital, Trichy, Tamilnadu, India

Consultant in Transfusion Medicine, Kauvery hospital, Trichy, Tamilnadu, India

*Correspondence: [email protected]

Background

Multiple myeloma is a clonal plasma cell disorder comprising 10% of haematological malignancies and accounts to 1% of all malignancies [1]. It has a male sex predilection affecting more African-Americans in comparison to Caucasians [2]. The median age of patients at the time of diagnosis is about 65 years [3]. Clonal plasmacytosis can be medullary or extramedullary and may cause hypercalcemia, renal failure, anemia and lytic bone lesions. Risk stratification is based on cytogenetics. Risk adapted initial therapy followed by autologous stem cell transplantation in eligible patients is the current standard of care. Initial induction therapy usually is a triplet regimen comprising of a proteosome inhibitor, immunomodulatory agent and steroid. Renal failure may add on to the existing complications of treatment in myeloma affecting overall survival.

Case Presentation

A 61-years-old male had pain involving legs, back and wrists persisting for six months duration. He had associated weight loss however he reported no trauma or fever. Evaluation revealed compression fracture involving D12. Bone marrow showed marked plasmacytosis in sheets. He had anemia, chronic kidney disease but no hypercalcemia. Creatinine clearance was 35 ml/min. Serum protein electrophoresis revealed M band, immunofixation revealed IgA lamda band and free light chain assay revealed lamda restriction. Fluorescent in situ hybridization (FISH) on bone marrow sample did not reveal del(17p) and conventional cytogenetics was normal. He was staged ISS category III.

He was started on CyBorD regimen consisting of Bortezomib, Cyclophosphamide, Dexamethasone given for six cycles. He showed a stringent complete response. Electrophoresis and immunofixation revealed no bands. Serum free light assay showed a normal kappa lamda ratio. Bone marrow revealed no clonal plasmacytosis.

Autologous stem cell transplantation was offered as a consolidation. Stem cell mobilization was done with granulocyte colony stimulating factor (G-CSF) and Plerixafor. Harvest was done uneventfully via a jugular hemodialysis catheter. Cell dose of 4.83 x 106/kg in a volume 270 ml.

Conditioning regimen administered was IV Melphalan 140 mg/sqm. Harvested stem cells were infused uneventfully after 48 hours. Fluconazole as antifungal prophylaxis and Acyclovir as antiherpetic prophylaxis were started since day +1. Mucositis was managed with supportive care and febrile neutropenia was managed with broad spectrum IV antibiotics. One dose pegylated G-CSF was administered on day +4. Weekly erythropoietin for renal failure was continued as before and two doses of Romiplostim was administered to accelerate platelet recovery. Irradiated platelet transfusions were administered to keep platelet count above 20000/cu.mm. Neutrophil engraftment (>500 cells/cu.mm) occurred on day +12 and platelet engraftment (>20000/cu.mm, unsupported since a week) occurred on day +16. He was discharged home on day +18 nce mucositis resolved completely. On day +60 post transplantation maintenance is planned to be started.

Discussion

Myeloma is currently treated with a triplet regimen comprising of proteosome inhibitor, immunomodulatory agent and steroid Dexamethasone. Novel agents have shown a significant improvement after their introduction. However, in patients with renal failure, CyBorD regimen is also an attractive option. It may reduce chances of neutropenia in comparison to VRD regimen with Lenalidomide. Wherever possible transplant eligible patients must be offered autologous stem cell transplantation after an initial risk adapted therapy to achieve a partial response or greater [1]. Renal failure should not constitute a criterion for exclusion from transplant unless patients display poor performance status and very high creatinine levels (>5 mg/dl) [4].

References

  • Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk‐stratification and management. Am J Hematol. 2020;95(5):548–67.
  • Landgren O, Weiss BM. Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis. Leukemia. 2009;23(10):1691–7.
  • Landgren O, Weiss BM. Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis. Leukemia. 2009;23(10):1691–7.
  • San Miguel JF, Lahuerta JJ, Garcia-Sanz R, Alegre A, Blade J, Martinez R, et al. Are myeloma patients with renal failure candidates for autologous stem cell transplantation? J Eur Haematol Assoc. 2000;1(1):28–36.

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