There are limited data on post-transplant lymphoproliferative disorder (PTLD) in the era of positron emission tomography (PET) and rituximab (R). Furthermore, there is limited data on the risk of graft rejection with modern practices in reduction in immunosuppression (RIS). We studied 91 patients with monomorphic diffuse large B-cell lymphoma PTLD at 11 Australian centers: median age 52 years, diagnosed between 2004 and 2017, median follow-up 4.7 years (range, 0.5–14.5 y). RIS occurred in 88% of patients. For patients initially treated with R-monotherapy, 45% achieved complete remission, rising to 71% with the addition of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP) for those not in complete remission. For patients initially treated with R-CHOP, the complete remission rate was 76%. There was no difference in overall survival (OS) between R-monotherapy and R-chemotherapy patients. There was no difference in OS for patients with systemic lymphoma (n = 68) versus central nervous system (CNS) involvement (n = 23) (3-y OS 72% versus 73%;
P
= 0.78). Treatment-related mortality was 7%. End of treatment PET was prognostic for patients with systemic lymphoma with longer OS in the PET negative group (3-y OS 91% versus 57%;
P
= 0.01). Graft rejection occurred in 9% (n = 4 biopsy-proven; n = 4 suspected) during the entire follow-up period with no cases of graft loss. RIS and R-based treatments are safe and effective with a low likelihood of graft rejection and high cure rate for patients achieving complete remission with CNS or systemic PTLD.
Alectinib is an orally bioavailable anaplastic lymphoma kinase (ALK) inhibitor indicated for ALK mutated non-small cell lung cancer (NSCLC). This case series documents the development of significant erythrocyte membrane changes associated with alectinib use in six patients. Morphological findings found on blood film examination include moderate-marked acanthocytes, spheroacanthocytes, and one case demonstrated moderate schistocytes. Two patients in this multi-centre case series developed grade 1 anaemia, and four patients developed grade 2 anaemia. Two patients suffered significant non-immune-related haemolysis. One patient had a co-existing β thalassaemia trait and required treatment cessation due to severe haemolysis. Low-grade anaemia was seen in 22% of patients using alectinib in the ALEX trial and 5% developed ≥ grade 3 anaemia. Alterations in erythrocyte morphology and membrane structure have not been reported in the safety data and clinical trials to date. Drug-induced acanthocytosis is a rare phenomenon and has previously been reported with high-dose prostaglandin administration only. This case series highlights this important laboratory finding with alectinib use and associated clinical sequelae. Alectinib-associated acanthocytosis is likely to be more prevalent than previously recognised. We also highlight the need for vigilance in haematopathology departments for unexpected laboratory findings associated with novel therapies. These findings can be detected in the post-marketing surveillance phase and may have serious clinical implications for patients.
Somatic malignant transformation of germ cell tumours is a well-described but poorly understood phenomenon. It is characterized by differentiation of pluripotent teratoma cells into somatic tumour cells. Following malignant transformation, the most common histologies are sarcomas and primitive neuroectodermal tumours; however, other subtypes have been recognized including melanoma, leukaemia, and renal cell carcinoma. We report a case of a 38-year-old male who had recently completed treatment for a mediastinal germ cell tumour with teratomatous components. He presented several months after completion of chemotherapy with metastatic lesions in his spine and liver accompanied with severe pancytopenia. He was subsequently diagnosed with acute megakaryoblastic leukaemia (AMKL), and a biopsy of a liver lesion was consistent with metastatic melanoma. This case illustrates the simultaneous development of 2 rare malignant entities: mediastinal germ cell tumour-associated AMKL and somatic malignant transformation to melanoma. It also highlights the importance of close surveillance to detect these metastatic sequelae and the emerging role of tumour sequencing to establish targetable pathways.
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