Canadian real-world experience of asciminib treatment in heavily pre-treated chronic myeloid leukemia (CML) patients who failed multiple lines of tyrosine kinase inhibitor (TKI) therapy.

BACKGROUND: Asciminib is a novel drug specifically targeting ABL myristoyl pocket in the ABL1 protein. METHODS: Forty one patients with chronic myeloid leukemia treated with asciminib from 2018 to 2022 were reviewed and analyzed for the efficacy and tolerability of asciminib using real-world experience data. RESULTS: The median age was 60 years (range 17-90) with a past history of a cardiovascular event in 21 patients (51%). Patients were pretreated with a median of 3 previous tyrosine kinase inhibitors (range 1-5). After a median of 12 months of asciminib (range 3-41), major molecular response (MMR) rate was 39% (n = 11/28) and 42% (n = 5/12) at 6 and 12 months, respectively. Molecular response with 2 log reduction (MR2) was noted in 54% (n = 15/28) and 50% (n = 6/12) at 6 and 12 months. The cumulative incidence of MMR and MR2 was 46.3% and 66% at 12 months. Five patients discontinued asciminib due to treatment failure (n = 3) or thrombocytopenia (n = 2). There were no cardiovascular events. Out of 7 patients treated with high dose asciminib for T315I mutation, 5 patients achieved MMR or deeper response. The event-free survival was 63% at 12 months. CONCLUSION: This study confirmed clinical efficacy and tolerability of asciminib with real-world experience.

Disseminated cryptococcal infection in a patient with treatment-naïve chronic lymphocytic leukemia (CLL).

We report a case of disseminated cryptococcosis in a treatment-naïve chronic lymphocytic leukemia (CLL) patient. A 60-year-old man presented with a two-week history of intermittent fevers, frontal headaches, night sweats, weight loss and multiple pink papules on hands and face. Cryptococcemia was found by blood culture unexpectedly. Further investigation confirmed cryptococcal meningitis and skin disease. He responded to two week amphotericin B and flucytosine followed by four-week amphotericin B and fluconazole, three-month high dose fluconazole (800 mg/day), and maintenance fluconazole (400 mg/day) thereafter. CSF pleocytosis persisted until day 203 while cryptococcal antigen in the CSF persisted at day 334 of treatment.

Outcomes of both abbreviated hyper-CVAD induction followed by autologous hematopoietic cell transplantation and conventional chemotherapy for mantle cell lymphoma: a 10-year single-centre experience with literature review.

We retrospectively evaluated consecutive patients diagnosed with Mantle cell lymphoma (MCL) between 01 January 2000 and 31 December 2009. Eighty eight patients with MCL were included in the analysis of whom 46 (52%) received abbreviated Hyper-CVAD (a total of two cycles; with addition of Rituximab since 2005) with an intention of proceeding to autologous hematopoietic cell transplantation (auto-HCT), with a median age of 58 years. Response rate to induction at auto-HCT time was 89% and complete response was 61%. Forty four patients received an auto-HCT with a 5-year progression-free survival (PFS) and overall survival (OS) were 31.2% and 62.5%, respectively. There were 42 nontransplant eligible patients with a median age of 72 years, and 5-year PFS and OS were 0.0% and 39.9%, respectively. The median survival and PFS in the auto-HCT eligible group were 68 and 33 months, compared to 32 and 12 months in nontransplant eligible group, without a plateauing of the survival curves in either group. Treatment-related mortality in the auto-HCT eligible group was 10.9% (n = 5); two patients died during R-Hyper-CVAD and 3 (6.8%) experienced transplant-related mortality. An abbreviated R-Hyper-CVAD-based induction strategy followed by consolidative auto-HCT is feasible and provides moderate potential of long-term survival. Further research to define risk-adapted strategies; to optimize disease control, is required.

A single-institution analysis of the utility of pre-induction ejection fraction measurement in patients newly diagnosed with acute myeloid leukemia.

Anthracyclines, a standard component of induction therapy for acute myeloid leukemia (AML) are known to be cardiotoxic. Existing evidence supporting routine baseline pre-induction cardiac function testing is limited. We conducted a retrospective analysis of 119 consecutive patients diagnosed with AML at our center from 2009 to 2012. In the 76 patients for whom induction chemotherapy was planned, baseline ejection fraction measurements were rarely abnormal (four cases), and in none of these abnormal cases did the result change management decisions. Awaiting LVEF evaluation results led to a delay in chemotherapy administration by a mean of approximately 2 days at significant additional costs to the healthcare system. Routine baseline ejection fraction measurement should be abandoned as it does not change management, results in treatment delay and unnecessary healthcare expenditures. More selective baseline testing, preferentially in patients in whom there is a clinical reason of cardiac disease, should be pursued.

Langerhans cell sarcoma with an aberrant cytoplasmic CD3 expression.

Langerhans cell sarcoma is a rare and aggressive high grade hematopoietic neoplasm with a dismal prognosis. It has a unique morphological and immunotypic profile with a CD1a/ langerin/S100 + phenotype. T cell lineage markers except for CD4 in Langerhans cell sarcoma have not been documented previously. We report a case of 86 year-old male of Caucasian descent who presented with an enlarging right neck mass over 2 months with an underlying unknown cause of anemia. Computed tomography scan of the neck, chest and abdomen revealed generalized lymphadenopathy and mild splenomegaly suspicious for lymphoma. Diagnostic core biopsy performed on right neck mass revealed a possible T cell lymphoma with expression of T cell lineage specific marker CD3 but conclusive diagnosis could not be made due to insufficient core biopsy sample. Further excisional biopsy performed on a left inguinal node showed a hematopoietic neoplasm with features of Langerhans cell sarcoma with a focal cytoplasmic CD3 expression in 30-40% of the tumor cells. PCR for T cell receptor (TCR) gene rearrangement failed to demonstrate a clonal gene rearrangement in the tumor cells arguing against a T cell lineage transdifferentiation, suggesting an aberrant CD3 expression. To the best of our knowledge, this case represents the first report of Langerhans cell sarcoma with an aberrant cytoplasmic CD3 expression. VIRTUAL SLIDES: http://www.diagnosticpathology.diagnomx.eu/vs/2065486371761991.

Secondary Strongyloides stercoralis prophylaxis in patients with human T-cell lymphotropic virus type 1 infection: report of two cases.

Secondary ivermectin prophylaxis for strongyloidiasis in two patients with human T-cell lymphotropic virus type 1 (HTLV-1)-associated malignancies and fully treated complicated strongyloidiasis is described. Treatment was well tolerated and neither patient developed further manifestations of hyperinfection. As treatment failure for complicated strongyloidiasis has been documented in severely immunosuppressed patients, secondary prophylaxis may be indicated.