Rouslan Kotchetkov

Background/Objectives: Azacitidine (AZA) is the standard of care for patients with higher-risk Myelodysplastic Syndromes (MDS). There is limited real-life data, however, characterizing its efficacy and safety profile in elderly patients. Methods: We conducted a single-center retrospective cohort chart review to compare front-line AZA therapy in patients ≥75 years (elderly) vs. 80 years, and 41 were younger (median age: 69.4 years). Baseline demographic variables were similar between both groups. The majority of elderly patients (98%) received the full dose of AZA (75 mg/m²), compared with 90% of younger patients. The median number of AZA cycles was 8 (range: 2–69) in elderly and 7.75 (range: 1–96) in younger patients. Treatment delays occurred in 36.4% of elderly and 29.3% of younger patients, most commonly due to infection complications in both groups (p = 0.076). Disease control rates (complete remission + partial remission + stable disease) were 92.9% in the younger subgroup and 96.4% in the elderly subgroup (p = 0.154). Relapse occurred in 48.8% of younger patients and 40.0% of elderly patients. Median overall survival (OS) was 17.3 months for the younger subgroup, 15.7 months for the elderly subgroup (p = 0.771), and 11.9 months among patients >80 years (p = 0.381). Mortality rates and causes of death were similar between both subgroups. Most common causes of death included disease progression, sepsis, febrile neutropenia, and pneumonia. Conclusions: AZA monotherapy resulted in a high response rate and was well-tolerated in elderly patients with higher-risk MDS. These findings remain consistent in the real-world setting despite potential confounding factors that may contribute to inferior outcomes.

Introduction: Front-line therapy with Azacitidine (AZA) + Venetoclax (Ven) improved overall survival (OS) and remissions in acute myeloid leukemia (AML) patients ineligible for standard induction. Less is known about the outcome of AML treated with AZA + Ven in the “real world”. Methods: We assessed the comparative pattern of administration, tolerability, efficacy and safety of AZA vs. AZA + Ven administered at our cancer centre. We retrospectively reviewed all patients treated with AZA alone or AZA + Ven. Patients who received less than one cycle or proceeded with consolidative stem cell transplant were excluded. Results: A total of 53 patients, median age 77 years, received AZA, and 23 patients, median age 73 years, received AZA + Ven. Among those, 69% and 47.8% were ≥75 years old, respectively. Only 52% received Ven doses above 200 mg. Mean time on therapy was 13.1 months in AZA vs. 5.9 months in AZA + Ven. Treatment delays occurred in 22.6% of AZA and 34.8% of AZA + Ven patients, primarily due to infections and cytopenias. Neutropenia grade 3/4 occurred in 28.3% of AZA vs. 56.5% of AZA + Ven patients. Thrombocytopenia grade 3/4 occurred in 15.1% of AZA and 51.2% of AZA + Ven patients. Anemia grade 3/4 occurred in 5.7% of AZA vs. 30.4% of AZA + Ven patients. Moreover, 69.8% of AZA and 69.5% AZA + Ven patients reached stable disease/partial and complete remission. Median overall survival (OS) was similar: 18 months in AZA vs. 14 months in the AZA + Ven group, p = 0.905. Conclusions: In a community setting, the addition of Venetoclax to AZA did not improve overall survival or disease control, mainly due to low tolerability and higher toxicity. However, these results should be interpreted cautiously due to a significant imbalance in the cytogenetic risk profiles and lower tolerability in the combined group. This suggests the need for a larger study with adjusted analyses.

Cyclic thrombocytopenia (CTP) is a rare disorder characterized by periodic platelet fluctuation with substantial amplitude from low to high. Currently, there are no standardized guidelines on treatment, and patients with CTP generally do not respond to standard ITP treatments, including corticosteroids, splenectomy, and intravenous immunoglobulin. We present a case of chronic CTP who failed multiple therapies used for immune thrombocytopenia but had resolution of muco‐cutaneous bleeding with supportive platelet transfusion at platelet nadir. Eventually, the patient had normalization of the platelet count after she applied an oral preparation containing hyaluronic acid (Oralvisc) for concomitant osteoarthritis. The effect of Oralvisc on the platelet count retained after discontinuation of the drug. We suggest that supportive platelet transfusion at the nadir of thrombocytopenia is an effective management option in symptomatic patients. Anti‐inflammatory medications, suppressing bradykinin and leptin, may be applied to alleviate platelet fluctuation and improve symptoms.

BACKGROUND: We assessed 93 hematology referrals of patients with undifferentiated lymphocytosis, focusing on patient experience and costs for both patients and the healthcare system. MATERIALS AND METHODS: We conducted a retrospective, observational cohort study at the Royal Victoria Health Center in Barrie, Ontario, and the Hudson Regional Cancer Program, Canada. Data included the nature of referrals (primary vs. secondary lymphocytosis), flow cytometry (FC)-based diagnosis, number of visits, time spent, healthcare costs, and patient experience through anonymous questionnaires. RESULTS: Ninety-four percent of patients were referred by their family physicians. FC results revealed that 56% of patients had primary lymphocytosis. The remaining cases were secondary lymphocytosis, with 90% of secondary cases being smoking-related. Only two patients required therapy for a newly diagnosed lymphoproliferative disorder. The average number of visits in 2023 was 1.98; 20% of patients spending 3 h or more per visit, including travel and appointment time. The reason for referral was explained to 80% of patients. While 50% of patients were nervous about attending the cancer center, over 90% felt reassured after the initial hematology consultation and found the information clear and satisfactory. However, 30% of patients reported that the visits were both financially draining and time-consuming. The total healthcare cost in 2023 was $758.42 per patient, with the total expense of $31,095 for cases of secondary lymphocytosis that did not require referral. CONCLUSION: These findings highlight that implementing FC in family practice can help distinguish primary from secondary lymphocytosis, reducing unnecessary hematology referrals, and potentially lowering healthcare costs, saving time, and reducing patient stress. This approach could lead to improved efficiency in the delivery of care and better utilization of healthcare resources.

Introduction: Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal demyelinating disease of the central nervous system caused by the reactivation of the John Cunningham virus (JCV) in immunocompromised patients. Obinutuzumab is type II anti-CD 20 antibody, used in combination with venetoclax for chronic lymphocytic leukemia (CLL). Case Presentation: A 75-year-old female patient was diagnosed with PML after a short course of obinutuzumab and venetoclax started for a newly diagnosed CLL. There was no history of hepatitis B, C, or human-immunodeficiency virus. Quantitative immunoglobulin levels were normal. She completed four infusions of obinutuzumab and subsequently started venetoclax, ramping up dose. Five days after the last dose of obinutuzumab, she developed forgetfulness and irrational behavior. Simultaneously, she had a new onset of cough and dyspnea and was subsequently diagnosed with a COVID-19 infection. One week later, her neurological condition began to deteriorate. Neurological examination did not reveal any focal neurological deficits. Magnetic resonance imaging head showed a nonspecific white matter signal change extensively involving the left frontal lobe, crossing the corpus callosum into the deep white matter of the right frontal lobe. Analysis of the cerebrospinal fluid was positive for the JCV, leading to a diagnosis of PML. Following a single dose of intravenous immunoglobulin 0.4 g/kg, the patient had a transient improvement of symptoms but subsequently deteriorated and died 1 month later. Conclusion: PML is a rare complication of anti-CD 20 monoclonal antibodies, including obinutuzumab. Early recognition of PML is essential to discontinue an affecting drug and initiate therapy.

Background: Essential Thrombocythemia is a chronic myeloproliferative neoplasm characterized by an isolated excessive production of platelets. Extreme thrombocytosis is defined by having a platelet count greater than or equal to 1,000 x 10⁹/L, which may lead to the development of acquired von Willebrand syndrome and complications of excessive hemorrhage.Case description: A 74-year-old female patient was brought in for a bone marrow examination regarding elevated platelet count. She had no history of excessive bleeding. The physical exam was unremarkable with no petechiae or hematomas. Complete blood count showed platelet count 1,491x10⁹/L. Bone marrow aspiration and biopsy were unremarkable, however, the patient developed bleeding from the biopsy site. Local pressure and an ice pack were ineffective, so she received 20 mcg of desmopressin subcutaneously, 1 unit of fresh frozen plasma and was started on tranexamic acid 1,000 mg orally every 8 hours. She was admitted for bleeding control and had another dose of desmopressin. Blood work showed elevated partial thromboplastin time and normal international normalized ratio. Acquired von Willebrand syndrome was suspected and a sample for von Willebrand disease was sent out. The next day her bleeding continued, and her Hb decreased from 145 to 89 g/L, she became symptomatic (tachycardic) and fatigued. The coagulation profile was consistent with acquired von Willebrand syndrome. Since she continued bleeding, she received 1 unit of packed red blood cells. A high dose of hydroxyurea (3g/day) was started urgently; within 24 hours platelet count was halved, and the bleeding resolved. Blood work was repeated 24 hours later and showed normalization of partial thromboplastin time and a normal Von Willebrand profile.Conclusion: Patients with extreme thrombocytosis are at high risk of bleeding due to acquired Von Willebrand Syndrome. Initiation of hydroxyurea at the time of bone marrow exam helps to control platelet count and minimizes the risk of peri-procedural hemorrhage in high-risk Essential Thrombocythemia patients with suspected acquired Von Willebrand Syndrome.

Introduction: Non-secretory multiple myeloma (NSMM) is a rare form of multiple myeloma (MM) that is often difficult to detect and has not yet been well characterized. This is due to the lack of production or the presence of monoclonal protein (MP) levels below levels detectable by testing such as serum/urine electrophoresis and immunofixation. Case Presentation: Two patients of ours were being treated for MM with typical courses of systemic therapy. By the third-line therapy, both developed an extramedullary mass, one in the pelvis and the other in the neck. In both cases, blood work showed no measurable MP, normal free light chain levels, and unremarkable skeletal surveys. Secondary malignancies were suspected due to the clinical presentation in each case, and biopsies confirmed the presence of non-secretory plasmacytomas. Both patients were only treated with localized radiotherapy with a total dose of 2,000 cGy in 5 fractions over 1 week. Ultimately, this resolved the original masses with no residual tumors. No changes had to be made to their systemic therapies, and both patients remained stable. Conclusion: NSMM relapse is not unusual and should be suspected in patients with relapsed refractory disease. Relapse should be confirmed by a tissue biopsy, and secondary malignancies should be ruled out. Radiotherapy is an excellent option to treat localized relapse and preserve the current line of systemic anti-myeloma therapy.

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.

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.