#3035 Nephrotic syndrome that changed the course of chronic myeloid leukemia treatment

Abstract Background and Aims An unusual instance of membranous nephropathy (MN) that developed concurrently with tyrosine kinase inhibitor (TKI) treatment for chronic myeloid leukemia (CML) is reported in this case. Hematologic malignancy and glomerular pathology management together posed a special treatment challenge that called for a creative multidisciplinary strategy. Method and Results After being diagnosed with CML, a 45-year-old woman was started on imatinib and achieved complete hematologic remission. However, two months after initiating TKI therapy, she developed nephrotic syndrome (NS). Kidney biopsy revealed MN. Serum anti-PLA2R were negative. Given the severity of her condition, a combined immunosuppressive regimen of systemic corticosteroids and cyclophosphamide was initiated. Recognizing the association between TKI therapy and NS, second-generation TKIs (bosutinib, followed by dasatinib) were trialed sequentially, but both resulted in recurrent NS. Complete remission of MN was achieved only after discontinuing TKI therapy while continuing immunosuppressive treatment. Due to contraindications for further TKI use, allogeneic hematopoietic stem cell transplantation (alloHSCT) was performed, with interferon-alpha used as an interim cytoreductive therapy. Long-term follow-up post-transplant revealed sustained molecular remission of CML and no recurrence of MN. The patient remains in complete remission of both conditions without requiring maintenance medication, and no signs of MN relapse or graft-versus-host disease (GVHD) have been observed. Conclusion This case of MN associated with CML raises important questions regarding the pathophysiological link between TKI therapy and glomerular injury. The favorable clinical outcome, marked by sustained remission of both CML and MN, without GVHD or maintenance therapy, suggest that TKI were probable culprit in this case. This case underscores the importance of strategic therapeutic planning and coordinated multidisciplinary care in managing complex hematologic conditions with significant renal complications.