Isoniazid: A Potential Culprit in Delayed Engraftment
Introduction/Background/Significance: Autologous stem cell transplant (ASCT) is essential in Multiple Myeloma to increase progression free survival. After graft infusion, Neutrophil engraftment typically occurs by Days 10–14 and platelet engraftment occurs by Days 14–21. This case proposes a potential association between isoniazid (INH) use and delayed engraftment after ASCT.
Materials and Methods/Case Presentation/Objective: A 57-year-old female presented with severe pelvic pain, following which an 8.6 × 3.5 cm Plasmacytoma was found in the superior pubic ramus, and she was diagnosed with Stage II IgG Lambda Multiple Myeloma. She began DVRd (Daratumumab, Bortezomib, Lenalidomide, dexamethasone). After seven cycles of DVRd, she attained complete remission with a Hemoglobin (Hb) 11.4 g/dL, White blood cells (WBC) 8.9, and PLT 184 (×109/L). Pretransplant evaluation for ASCT included a positive QuantiFERON-TB Gold, and a 6-month course of INH for Latent Tuberculosis (TB) was initiated. After a month, the patient received conditioning chemotherapy with Melphalan 200mg/m2, followed by graft infusion with 10 ×106 CD34+ cells/kg of 59% viability. On Day -1, Hb 9.2 g/dL, WBC 3 with absolute neutrophil count (ANC) of 2.7, PLT 197 (×109/L). Day +3 Hb 8.8 g/dL, WBC 0.4, ANC 0.3, PLT 85 (×109/L). Despite Tbo-filgrastim (G-CSF) post-transplant for neutropenia, engraftment had still not occurred by Day +14, and she remained severely pancytopenic with Hb 7.4 g/dL, WBC 0.0, and PLT 8 (×109/L), requiring transfusions. Subsequent testing, including Erythropoietin level, CMV, EBV, HHV-6, Bone marrow Biopsy, FISH, MDS FISH panel, Vitamin B12, copper, and Zinc, was unremarkable. Pathology did note some elements of marrow recovery. Meanwhile, INH was held on Day +15. The patient's WBC started to increase on Day +16, from 0 to 0.1, and WBC engraftment occurred on Day +19, with ANC and WBC at 0.6 ×109/L. Eltrombopag was started on day + 20 to aid in PLT and to decrease transfusion requirements after stem cell transplant. From Day 21 to Day 24, and subsequently to Day 32: Hb 7.7à 8.1à 8.1 (g/dL), WBC 1.8à 8.2 à 3.7, ANC 1.7à 7.6à3.1, PLT 5à 12à 71 (×109/L). INH was temporarily withheld, and she remained on G-CSF and eltrombopag.
Results/Description/Main Outcome Measures: INH causes Sideroblastic anemia and immune-mediated thrombocytopenia. However, it is not documented to cause delayed engraftment after ASCT and has been relied upon to prevent TB reactivation without affecting graft outcomes in prior retrospective studies. In this patient, failure of counts to improve despite G-CSF, until withholding INH raised suspicion of its possible role in delayed engraftment, given the extensive workup for other potential causes was unremarkable. Although PLT improved after holding INH, she required intermittent transfusions, leading to the initiation of eltrombopag with marked improvement. It was initiated after WBC had already begun to recover and may have contributed to further WBC improvement thereafter.
Conclusions: This case presents a unique scenario after ASCT, prompting careful consideration of INH as a potential cause of graft delay and the need to exercise caution in the use of all medications post-stem cell transplantation. This also highlights the need for prospective studies on the effects of INH in post-transplant patients.
