The characteristics of CALR mutations in myeloproliferative neoplasms: a clinical experience from a tertiary care center in Qatar and a literature review.

BACKGROUND: Myeloproliferative neoplasms (MPNs) are hematological disorders characterized by abnormal production of myeloid cells due to genetic mutations. Since 2013, researchers have identified somatic mutations in the Calreticulin (CALR) gene, primarily insertions or deletions, in two Philadelphia chromosome-negative MPNs; essential thrombocytosis (ET) and primary myelofibrosis (PMF), and occasionally in chronic myelomonocytic leukemia (CMML). This study aims to identify the various types of CALR mutations and their impact on CALR-positive MPN patients' clinical manifestations and outcomes. METHODS: A single-center retrospective study was conducted. The data was collected from pre-existing records. The study was carried out on Philadelphia-negative MPN patients who were being followed up on at the NCCCR (National Center for Cancer Care and Research) to assess the clinical manifestation and outcome of disease treatment. All patients included, were followed in our center between January 1, 2008, and November 20, 2021. RESULTS: A total of 50 patients with CALR-positive MPN were reviewed with a median follow-up of three years (1-11). This cohort included 31 (62%) patients with ET, 10 (20%) patients with PMF, and 9 (18%) patients with prefibrotic myelofibrosis (pre-MF). The study involved 38 (76%) male and 12 (24%) female patients. There were 16 (32%) patients diagnosed before the age of 40, 24 (48%) patients diagnosed between the ages of 40 and 60; and 10 (20%) patients diagnosed after the age of 60. Molecular analysis showed 24 (48%) patients with CALR type 1, 21 (42%) patients with CALR type 2, and 5 (10%) patients with none Type 1, none Type 2 CALR mutations. Two patients have double mutations; 1(2%) with none Type 1, none Type 2 CALR and JAK2 mutations, and 1(2%) with CALR type 1 and MPL mutations. The thrombotic events were 3 (6%) venous thromboembolisms, 3 (6%) abdominal veins thromboses, 2 (4%) strokes, and 4 (8%) ischemic cardiac events. Only 4 (8%) patients progressed to Myelofibrosis and were carrying CALR 1 mutations, and 1 (2%) patient progressed to AML with CALR 2 mutation. CONCLUSION: The data shows a significant rise in CALR-positive MPN diagnoses in younger people, emphasizing the need for a better assessment tool to improve disease management and reduce complications.

Acute Myeloid Leukemia in Qatar (2010-2016): Clinical, Biological, and Prognostic Factors and Treatment Outcomes.

The current study retrospectively evaluated cytogenetic profiles, various prognostic factors, and survival outcomes in 128 acute myeloid leukemia (AML) patients (14 ≤ age ≤ 70 years) admitted to the National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation, Doha, Qatar, between January 2010 and December 2016. The median age at diagnosis was 43 years, and 80% were less than 60 years old; 75% of patients were male. Cytogenetic analysis was integrated into the World Health Organization 2008 classification and showed that the percentages of normal and abnormal karyotypes were similar, accounting for 48.4% of each group of patients. The AML risk stratification based on cytogenetic analysis resulted in the following distribution: 18% in the favorable risk group, 57% in the intermediate-risk group, 24% in the unfavorable risk group, and 1% unknown. Only 88 patients received therapy with curative intent; 67% achieved complete remission, increasing to 81% after inductions 1 and 2. The median overall survival (OS) and disease-free survival (DFS) in AML patients were 26.6 and 19.5 months, respectively. The 3-year OS and DFS were 40 and 36%, respectively. Prognostic factors including age, gender, white blood cell count, and risk stratification were not significantly associated with treatment outcomes, whereas response to treatment vs. failure was significantly associated with the outcome (p = 0.01). The current study supports the importance of cytogenetics as a useful tool in diagnosis, prognosis, and risk assessment in AML treatment.

A Rare Case of Systemic Mastocytosis with Associated Hematologic Neoplasm (SM-AHN) Involving Chronic Myeloid Leukemia: A Case Report and Literature Review.

BACKGROUND Single or multiple cell line dysplasia is a characteristic feature of myelodysplastic syndrome. However, significant dysgranulopoiesis is not a feature of chronic myeloid leukemia (CML). Systemic mastocytosis (SM) with an associated hematologic neoplasm (SM-AHN) comprises 5% to 40% of cases of SM. All types of hematologic neoplasms have been previously reported, although CML has been rarely encountered. CASE REPORT A 28-year-old male presented with a 3-month-history of weight loss and massive splenomegaly. Peripheral blood revealed marked leukocytosis, shift to left with 13% blasts. There was evident dysgranulopoiesis that raised a provisional diagnosis of myelodysplastic/myeloproliferative neoplasm. Bone marrow (BM) examination revealed granulocytic hyperplasia with 10% blasts and significant dysgranulopoiesis. Unexpectedly, cytogenetic analysis revealed t(9;22) with BCR/ABL1 rearrangement, diagnostic of chronic myeloid leukemia in an accelerated phase. The patient was started on dasatinib 100 mg upfront, however, he failed to respond, with increasing leukocytosis. Repeat BM examination showed persistence of the findings with 8% blasts. At this time, aggregates of mast cells with aberrant expression of CD25 were elicited, thus concluding the diagnosis of SM-AHN. The patient failed multiple lines of treatment (dasatinib, nilotinib, hydroxyurea, cytarabine subcutaneous, 6-mercaptopurine and interferon) and progressed to the blast phase a few months later. CONCLUSIONS We report an unusual case of CML, presented with significant dysgranulopoiesis with an aggressive clinical course including SM uncovered during the disease course with subsequent transformation to the blast phase. The different biological behavior of this case underscores the need for studies on a larger number of cases to explore the significance of the aforementioned coexistent features.