Clinical Features and Long-Term Outcomes of a Pan-Canadian Cohort of Adolescents and Young Adults with Myeloproliferative Neoplasms: A Canadian MPN Group Study.

Myeloproliferative neoplasms (MPNs) are a group of chronic hematologic malignancies that lead to morbidity and early mortality due to thrombotic complications and progression to acute leukemia. Clinical and mutational risk factors have been demonstrated to predict outcomes in patients with MPNs and are used commonly to guide therapeutic decisions, including allogenic stem cell transplant, in myelofibrosis. Adolescents and young adults (AYA, age ≤45 years) comprise less than 10% of all MPN patients and have unique clinical and therapeutic considerations. The prevalence and clinical impact of somatic mutations implicated in myeloid disease has not been extensively examined in this population. We conducted a retrospective review of patients evaluated at eight Canadian centers for MPN patients diagnosed at ≤45 years of age. In total, 609 patients were included in the study, with median overall survival of 36.8 years. Diagnosis of prefibrotic or overt PMF is associated with the lowest OS and highest risk of AP/BP transformation. Thrombotic complications (24%), including splanchnic circulation thrombosis (9%), were frequent in the cohort. Mutations in addition to those in JAK2/MPL/CALR are uncommon in the initial disease phase in our AYA population (12%); but our data indicate they may be predictive of transformation to post-ET/PV myelofibrosis.

Delayed Diagnosis of T-Cell Prolymphocytic Leukemia: Approach to Chronic Lymphocytosis.

We present a case of lymphocytosis assumed and managed initially as a chronic lymphocytic leukemia. Shortly after initial visit, the patient's condition deteriorated rapidly with hepatosplenomegaly, pleural effusion, ascites, and skin lesions. Flow cytometry (FC) showed the presence of clonal T-cell population, reported as T-cell lymphoma. Due to rapid clinical deterioration, urgent therapy with cyclophosphamide, doxorubicin, vincristine, etoposide, prednisone was initiated, but with minimal response. This prompted further diagnostic testing and demonstrated tumor cells positivity for CD3, CD30, and TCL1 markers. The diagnosis was changed to T-cell prolymphocytic leukemia. The patient responded well to alemtuzumab (anti-CD52 monoclonal antibody) and reached complete remission. FC is an essential modality for assessing and screening circulating lymphocytes when a lymphoproliferative disorder (LPD) is suspected. There are several LPDs that present with different degrees of clonal lymphocytosis. Reactive lymphocytosis should be appropriately investigated. Indolent LPDs can be surveyed by the internist or family physician, while more aggressive LPDs typically require management by hematologists.

Case Report: Effects of multiple myeloma therapy on essential thrombocythemia and vice versa: a case of synchronous dual hematological malignancy.

Background: Dual hematological malignancies, asynchronous or synchronous, are underrecognized entities and are usually suspected when clinical, hematological, or biochemical features cannot be explained by the primary malignancy alone. We present a case of synchronous dual hematological malignancies (SDHMs), where the patient was diagnosed with symptomatic multiple myeloma (MM) and essential thrombocythemia (ET), when excessive thrombocytosis occurred following initiation of MPV (melphalan-prednisone-bortezomib) antimyeloma therapy. Case description: An 86-year-old woman presented to the emergency in May 2016 with confusion, hypercalcemia, and acute kidney injury. She was diagnosed with free light chain (FLC) lambda and Immunoglobulin G (IgG) lambda MM and started MPV (standard of care at that time) treatment with darbopoietin support. At diagnosis, she had normal platelet count since the ET was likely masked by bone marrow suppression due to active MM. After she reached stringent complete remission with no MP detected on serum protein electrophoresis or immunofixation, we noticed that her platelet counts increased to 1,518,000 × 109/L. She was tested positive for mutation in exon 9 of calreticulin (CALR). We concluded that she had concomitant CALR-positive ET. After bone marrow recovery from MM, the ET became clinically apparent. We started hydroxyurea for ET. Treatment for MM with MPV did not affect the course of ET. Presence of concomitant ET did not decrease the efficacy of sequential antimyeloma therapies in our elderly and frail patient. Conclusion: The possible mechanism underlying the occurrence of SDHMs is unclear but is likely due to stem cell differentiation defects. SDHMs can be challenging to treat and warrant several considerations. In the absence of clear guidelines on how to manage SDHMs, management decisions depend on several factors including disease aggressiveness, age, frailty, and comorbidities.