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Lack of efficacy: case report A study described a 69-year-old man, who did not respond to hydroxycarbamide administered for the treatment of atypical chronic myeloid leukaemia. Additionally, he did not respond to amphotericin-B liposomal, isavuconazole and voriconazole administered for the treatment of pulmonary mucormycosis [routes and dosages not stated]. The man presented to hospital with a 4-month history of suspected diagnosis of a myelodysplastic/myeloproliferative neoplasm. Despite cytoreductive therapy with hydroxycarbamide [hydroxyurea], his WBC and ANC were poorly controlled and severe dysgranulopoiesis with hypogranularity was observed. The next generation sequencing analysis revealed the presence of mutations in 8 genes including the CSF3R p.T618I mutation. Due to the presence of dysgranulopoiesis with neutrophil precursors of >10%, he was diagnosed with atypical chronic myeloid leukaemia. Haematopoietic stem cell transplantation was deferred as a treatment option due to his advanced age and chronic kidney disease. Despite cytoreductive therapy with hydroxycarbamide [hydroxyurea], his WBC count and constitutional symptoms remained poorly controlled. Neutrophils displayed strongly impaired migration when compared to healthy controls and migrating cells exhibited a more flattened-out morphology than control neutrophils. Based on reports of the potential benefit of ruxolitinib in CSF3R T618I mutated myeloid neoplasms, he was initiated on off-label therapy with ruxolitinib 10mg twice daily (day 0). After 1 week of treatment with ruxolitinib, the cell shape normalised and remained indistinguishable from healthy control neutrophils. However, neutrophil migration did not improve. Treatment with ruxolitinib and hydroxycarbamide resulted in a drop in WBC count; however, when hydroxycarbamide was discontinued, the WBC count rapidly increased. Therefore, the dose of ruxolitinib was increased to 20mg twice daily and hydroxycarbamide was resumed, resulting in a drop in his WBC count (day 73). His WBC rose again when he was hospitalised due to sinusitis, fever and gastric ulcer bleeding. Two months later, his WBC rose again with an increasing percentage of myeloblasts (day 193). As a result, mercaptopurine was added to the ongoing hydroxycarbamide, following which his WBC count and percentage of myeloblasts decreased. However, on day 256, he was hospitalised again due to pneumonia and haemoptysis. In the subsequent weeks, he was diagnosed with pulmonary mucormycosis. Consequently, the man received amphotericin-B liposomal, isavuconazole and voriconazole. Despite the treatment with amphotericin-B liposomal, isavuconazole and voriconazole, he passed away on day 370 [immediate cause of death not stated]. Bornemann L, et al. Defective migration and dysmorphology of neutrophil granulocytes in atypical chronic myeloid leukemia treated with ruxolitinib. BMC Cancer 20: No. 1, 803517031 2020. Available from: URL: http://doi.org/10.1186/s12885-020-07130-7

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