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Melphalan can rarely cause interstitial pneumonitis and fibrosis. Although it has been reported previously in patients after conventional doses, we report four cases developing diffuse interstitial pneumonitis (DIP) after high-dose melphalan-based therapy. In a 3-year period, four of 57 (7%) consecutive patients undergoing high-dose melphalan (200 mg/m2; MEL 200) were identified with DIP. Two patients who were heavily pre-treated with alkylators developed progressive respiratory failure despite high-dose steroids and eventually died. The other two patients previously treated with vincristine, adriamycin, and dexamethasone (VAD) improved dramatically on high-dose steroids with complete resolution of their pneumonitis. Melphalan should be added to the growing list of alkylators causing pulmonary toxicity. Bone Marrow Transplantation (2000) 26, 1107–1109. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the outcome of high-dose therapy with autologous hematopoietic stem cell transplantation (HSCT) in patients with primary systemic amyloidosis reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). PATIENTS AND METHODS: A total of 107 recipients of autologous HSCT for amyloidosis from 48 transplantation centers were reported to the CIBMTR between 1995 and 2001. Hematologic and organ responses were assessed at 100 days and 1 year. Transplantation-related mortality (TRM) was assessed at day 30 after HSCT. A multivariate analysis assessed factors that influenced overall survival. RESULTS: Improvement at day 100 was seen in 1 or more amyloidosis-affected sites (bone marrow, kidney, liver, and/or heart) in 28 (36%) of 77 patients; the 1-year responses included complete response (16%), partial response (16%), stable disease (31%), and disease progression (10%). With a median follow-up of 30 months, the 1- and 3-year survival rates were 66% (95% confidence interval [CI], 56%-75%) and 56% (95% CI, 45%-66%), respectively. The day 30 TRM was 18% (95% CI, 11%-26%). In the multivariate analysis, only the year of transplantation (patients who most recently underwent transplantation) was associated with post-HSCT survival (P-.02). CONCLUSION: In this multi-institutional CIBMTR study, the 3-year survival rate was comparable to single-center results, with patients who more recently underwent transplantation faring better. Of note, the TRM was higher than that reported by single centers, which may reflect differences in patient selection and/or experience in treating this challenging disease. We hope that a better understanding of the recently recognized prognostic factors and more stringent patient selection will result in lower TRM and improved survival. [ABSTRACT FROM AUTHOR]

Introduction: Next-generation sequencing (NGS) of tumor DNA can detect actionable drivers and help guide therapy for patients with advanced-stage cancers. While tissue-based genotyping is considered a standard of care, blood-based genotyping is emerging as a valid alternative. Tumor genomic profiles may vary by region, and data from the Middle East and North Africa (MENA) are not widely available. This study elucidates the genomic landscape of advanced solid cancers in patients from the MENA region by retrospectively analyzing results from NGS circulating tumor DNA (ctDNA) testing., Methods: In routine clinical practice, 926 plasma samples from 767 patients with advanced cancers from the MENA region were profiled using a comprehensive NGS assay (Guardant360®). We conducted a pan-cancer analysis and sub-analyses focusing on lung, breast, and colorectal cancers., Results: In the pan-cancer group, TP53 (58.5%), EGFR (20.4%), and KRAS (18.9%) were the most frequently mutated genes. EGFR (10.2%), FGFR1 (4.9%), and PIK3CA (4.9%) showed the most amplifications, while fusions were observed in 2.7% of patients, including ALK, FGFR2, and RET. For lung adenocarcinoma, EGFR (30.5%), KRAS (19.3%), and ERBB2 (4.6%) were the most frequently identified alterations among the genes recommended for evaluation by the National Comprehensive Cancer Network (NCCN). In patients with breast cancer, PIK3CA (35.3%), ESR1 (21.7%), and BRCA1/2 (13.3%) had the most prevalent alterations among NCCN-recommended genes. In colorectal cancer, KRAS (39.0%), NRAS (8.0%), and BRAF (V600E, 4.0%) were the most observed mutations among genes recommended by the NCCN. Comparing this cohort to publicly available Western and Eastern datasets also indicated similarities (including PIK3CA in breast cancer) and variances (including EGFR in lung adenocarcinoma) in key genes of interest in the analyzed cancer types., Conclusion: Overall, our findings provide insight into the genomic landscape of individuals with advanced solid organ malignancies from the MENA region and support the role of ctDNA in guiding therapeutic decisions., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Tumour lysis syndrome (TLS) in plasma cell dyscrasias is extremely rare. TLS has been described in eight cases of multiple myeloma undergoing high-dose therapy with autologous stem cell transplant (ASCT). Recently, clinical trials of intensive chemotherapy followed by autologous or allogeneic stem cell support has been shown to offer potential benefit in AL (amyloid light-chain) amyloidosis. TLS in primary AL amyloidosis in this setting has not been previously reported. We report a case of TLS in a patient with AL amyloidosis which developed after high-dose melphalan chemotherapy supported by ASCT.