Chronic Lymphocytic Leukemia in Pregnancy: A Review of the Available Literature and the Pharmacological Challenges in Management.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a rare hematologic malignancy to occur in pregnancy, with an estimated incidence of 1 in 75,000 pregnancies. Pregnant women with CLL face increased susceptibility to infections, due to a weakened immune system. Higher risks of fetal malformations and death are associated with CLL treatment during pregnancy, emphasizing the need for careful consideration and management in these cases. SUMMARY: This review aimed to summarize the current evidence regarding the diagnosis, prognosis, and treatment of CLL in pregnant cases. A comprehensive search strategy was employed across multiple databases, yielding 14 case reports for inclusion. The cases were divided based on CLL diagnosis onset, either before or during pregnancy. Our results showed that patients diagnosed during pregnancy (n = 5) were mostly asymptomatic at diagnosis, with management ranging from supportive care to leukapheresis and transfusions. Postpartum treatment varied, with some patients requiring no additional therapy and others receiving chemotherapy. Pregnancy outcomes were generally favorable, with most neonates born healthy at term. However, one case of Richter transformation resulted in maternal death despite treatment. Among patients with pre-existing CLL (n = 9), the majority experienced an indolent course during pregnancy, with only supportive care required. A few cases necessitated treatment due to progressive disease or complications, including chemotherapy, leukapheresis, and splenectomy. KEY MESSAGES: This review highlights the heterogeneous nature of CLL in pregnancy and the importance of individualized management based on disease severity, gestational age, and maternal-fetal risks. Close monitoring, supportive care, and a multidisciplinary approach are essential for optimizing outcomes in this rare and complex clinical scenario.

Establishment of a Clinical Pharmacist-Led Multiple Myeloma Clinic with Collaborative Prescribing Model at the National Center for Cancer Care and Research in Qatar.

BACKGROUND: Multiple Myeloma (MM) is a chronic and incurable hematologic malignancy that is prevalent among the elderly. Interprofessional patient care showed superiority over physician-only care in multiple settings, including MM. OBJECTIVE: The primary objective of this study was to evaluate the impact of CP-led clinic and CPs interventions on MM patient care. PRACTICE DESCRIPTION: Real-world analysis of ambulatory patients with MM showed that clinical pharmacists (CPs) were central to the optimization of therapy and adherence to treatment schedules and supportive medications. PRACTICE INNOVATION: The CP-led MM Clinic was established with a collaborative prescribing agreement (CPA) in 2022 at the National Center for Cancer Care and Research (NCCCR) in Qatar and was the first of its kind in the MENA region. This CPA allowed CPs to issue refills for supportive medications and order required laboratory tests. EVALUATION METHODS: Data collected included the number of CP interventions, refills ordered by CPs, documentation of patient education, and medication reconciliations. The data were retrospectively collected and analyzed comparing ambulatory patients with MM treated before (2021) to those treated after the clinic implementation in 2022. RESULTS: The study population comprised 20 patients. A higher number of CPs interventions were documented post-clinic than pre-clinic (343 vs. 76, P=0.004), with earlier initiation of bisphosphonate post-clinic (25 vs. 206 days, P = 0.008). There were also significant improvements in the introduction of risk appropriate venous thromboembolism (VTE) prophylaxis (43% vs. 6%, P=0.001) as well as vitamin D and calcium supplementation (100% vs. 68%, P=0.02) post-clinic. Twenty-two medication refills for supportive medications and eight pre-chemotherapy laboratory investigations were ordered by CPs. CONCLUSION: The CP-led clinic provided a timely link to care optimization for ambulatory MM patients. This innovative CPA model implemented in the clinic could potentially be applied to different cancer settings to optimize safe and effective patient care.

Carfilzomib-induced life-threatening lung injury in refractory multiple myeloma.

INTRODUCTION: Carfilzomib is a second-generation selective proteasome inhibitor that is commonly used in the treatment of relapsed or refractory multiple myeloma. Carfilzomib is associated with respiratory side effects, such as cough, dyspnea, and upper respiratory tract infection. However, severe pulmonary toxicity is rare and is only reported in a few case reports. CASE REPORT: Here, we present a case of a 65-year-old male with refractory multiple myeloma who developed a life-threatening lung injury during his third cycle of carfilzomib. The patient presented with a decreased level of consciousness and was found to have Type I respiratory failure. He was admitted to the intensive care unit, where he was intubated. Blood cultures and viral panel were negative. The patient received a prolonged course of antibiotics with 2 days of hydrocortisone. MANAGEMENT AND OUTCOMES: After discharge, repeated myeloma workup showed disease progression and carfilzomib was reintroduced. The next day, he presented with fever, vomiting, and hypoxia. Chest x-ray showed congestive lung changes with patchy airspace opacities. Repeated echocardiography showed normal ejection fraction with moderate pulmonary hypertension (RVSP 46 mm Hg). The patient was transferred again to the ICU and kept on continuous positive airway pressure. Antibiotics were started, and blood cultures and respiratory viral panels were negative for any infectious organism. The patient improved in terms of inflammatory markers and oxygen requirements. Treatment with carfilzomib was stopped permanently. DISCUSSION: Pulmonary toxicity associated with carfilzomib in patients with multiple myeloma can be potentially life-threatening. The mechanism with which carfilzomib induces lung-related AEs is still not fully understood. In our patient, carfilzomib-induced lung injury was evident after rechallenging the patient with carfilzomib, in the radiographic x-ray changes and the new onset moderate pulmonary hypertension. Healthcare providers should be encouraged to report rare adverse events in order to identify the risk factors that can predispose patients to the development of these adverse events.

Effects of Intermittent Fasting on Response to Tyrosine Kinase Inhibitors (TKIs) in Patients With Chronic Myeloid Leukemia: An Outcome of European LeukemiaNet Project.

The overall survival of patients with Chronic Myeloid Leukemia (CML) treated by using tyrosine kinase inhibitors (TKIs) is very close to that of the healthy population. However, little is known about the effect of specific measures such as intermittent fasting, especially during Ramadan period. A 3-year retrospective study was conducted to evaluate the effect of fasting on patients with CML receiving TKIs by evaluating certain clinical, hematological, and molecular parameters. A total of 49 patients were eligible, with a median age of 46 years (range: 22-86), of these 36 (73.5%) were males and 13 (26.5%) were females. Twenty-seven (55%) patients are Middle Eastern, while 16 (32.7%) from the Indian subcontinent, and 6 (12.3%) Africans. Imatinib was the most common TKI; used in 25 patients (51%). The mean White blood cells (WBCs), neutrophils, and BCR-ABL were found to be reduced after fasting compared to before and during with statistical difference. The use of TKIs while fasting did not result in significant changes in hematological nor BCR-ABL levels in our study. Patients who wish to practice intermittent fasting may be reassured in this regard, yet physicians can adopt the safe trial approach, where they allow the patients to fast, but with instructions such as when to break fasting.

Disseminated tuberculosis after Polatuzumab-Vedotin based chemoimmunotherapy in a patient with Burkitt's lymphoma.

This report highlights the risk of latent tuberculosis (TB) reactivation after treatment with Polatuzumab Vedotin (PV), Rituximab, and Bendamustine (PBR protocol) despite appropriate chemoprophylaxis. A 48-year-old male with refractory Burkitt's lymphoma (BKL) was treated with PBR protocol. At baseline, the patient had a negative QuantiFERON test result, which turned out to be positive prior to starting PBR. He received chemoprophylaxis for 9 months and was compliant with treatment. One year later, he was admitted with COVID-19 pneumonia and was treated according to the protocol. His symptoms persisted for 1 month. Investigations yielded disseminated TB-infiltrated bone marrow and pleura. Downstream B-cell and T-cell depletion secondary to CD20 and CD79b antagonism may potentially explain the increased risk of TB reactivation associated with the combination of PV and rituximab. Further research is necessary to monitor the risk of TB reactivation among patients receiving a combination of PV and rituximab, especially in endemic areas with high prevalence and incidence of TB.

Venetoclax in the treatment of secondary plasma cell leukemia with translocation t(11;14): a case report and literature review.

Introduction: Venetoclax is a BCL-2 inhibitor with proven efficacy in patients with multiple myeloma (MM) and translocation t(11;14). However, its role in plasma cell leukemia (PCL) remains unclear. Herein, we aimed to report a case of relapsed MM with secondary PCL and t(11;14) achieving complete (CR) and durable remission with venetoclax therapy. Case presentation: A 52-year-old gentleman was diagnosed with MM-free light chain lambda (ISS III) in December 2016. He received induction therapy, followed by autologous stem cell transplant. (ASCT) in May 2017 and maintenance. A year later, the patient relapsed with secondary PCL. His cytogenetics analysis revealed t(11; 14). The patient failed salvage chemotherapy and was shifted to venetoclax with dexamethasone treatment. The patient attained complete remission (CR), which was maintained for two years and a half before he developed fatal COVID-19 pneumonia. Conclusion: In comparison with the reported literature, this case report offers the latest compilation of the available evidence on the use of venetoclax in patients with PCL. Furthermore, our patient achieved CR for the longest reported durable response in literature thus far. Prospective clinical trials are needed to elucidate the optimal dosage, combination, and duration of treatment, ensuring better representation and generalizability of the findings. Meanwhile, venetoclax may be considered as a therapeutic option in patients with PCL t(11;14).

The Safety of Novel Therapies in Chronic Lymphocytic Leukemia in the Era of Intermittent Fasting: A Pharmacology-Based Review.

Intermittent fasting (IF) has recently gained popularity due to its emerging benefits in reducing weight and improving metabolic health. Concurrently, novel agents (NAs) like venetoclax and Bruton tyrosine kinase inhibitors (BTKIs) have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Unfortunately, it is unclear whether the associated risks of tumor lysis syndrome (TLS) and gastrointestinal bleeding (GIB) are increased in IF practitioners receiving NAs. This review explored the literature available on the permissibility of IF in CLL patients undergoing treatment with first-line NAs (FLNAs). Literature was scoped to identify IF patterns and the available data on TLS and GIB risks associated with food and fluid intake in CLL patients receiving FLNAs. Although current evidence is insufficient to recommend IF in this population, it may be possible for patients on venetoclax to conservatively practice fluid-liberal IF, provided that adequate hydration and the consistent administration of food are achieved. In contrast, considering the significant risk of TLS and the pharmacokinetics of venetoclax, patients should be discouraged from practicing fluid-restricted IF, especially during the ramp-up phase. Moreover, patients on BTKIs ought to refrain from IF due to the possible risk of GIB until further data are available. Further research is needed to provide conclusive recommendations.

Relapsed IgA Multiple Myeloma as Testicular Plasmacytoma after Quadrable Novel Therapy and Autologous Stem Cell Transplant: A Rare Case Report and Literature Review.

Introduction: Multiple myeloma (MM) is a clonal neoplasm of plasma cells that may manifest as an extramedullary disease in rare cases. Case Report: In this case report, we present the rare occurrence of testicular relapse in a 39-year-old patient with IgA MM after 3 years of remission. We discuss the clinical course and management of this unusual presentation and provide a comprehensive literature review of testicular involvement by MM. Conclusion: Despite advances in MM treatment, relapse remains common, highlighting the importance of careful follow-up and timely detection of disease recurrence at atypical sites. This case highlights the need for further research to standardize the diagnosis and treatment of testicular MM.

Skull base plasmacytoma in young patients aged below 40 years: Radiological perspectives and clinical outcomes.

BACKGROUND: Plasmacytoma of the skull base is a rare manifestation of plasma cell neoplasm with only a few cases documented in literature involving young adults. Plasmacytoma can be an isolated solitary lesion or a secondary manifestation of multiple myeloma (MM). In this study, we report the clinical and radiological characteristics, management, and outcomes of patients under the age of 40 who presented with skull base plasmacytoma and associated neurological manifestations. Additionally, we share our experience in treating a rare case of skull base plasmacytoma diagnosed during pregnancy, in which the patient exhibited a favorable response to myeloma treatment initiated after delivery. CASE SERIES: Four patients were identified, comprising one pregnant female and three male patients, with a median age of 36 years (range 33-37 years). The main presenting symptoms were headache, dizziness, and cranial nerve palsy. All patients received underwent systemic myeloma therapy and radiotherapy with three patients also underwent autologous stem cell transplantation (ASCT). Notably, all patients achieved complete remission. CONCLUSION: Skull base plasmacytoma represents a rare manifestation of plasma cell neoplasms, underscoring the importance of considering it in the differential diagnosis of skull base lesions to ensure early intervention and avoid potential serious complications. Throughout our series, the cornerstone of therapy involved radiotherapy, systemic myeloma therapy, and ASCT, all of which elicited a favorable response in every case.

Real world evidence of epidemiological trends, clinical presentation, and prognostic outcomes of multiple myeloma (2007-2021).

Background: Multiple myeloma (MM) is one of the most common hematological malignancies globally, and it is projected to increase in the coming years. It occurs more frequently in males and affects older individuals. Presenting symptoms can range from being asymptomatic to severely debilitating. The objective of this study was to determine the epidemiology, clinical features, and prognostic outcomes of patients with MM in the only tertiary cancer hospital in Qatar. Methods: Patients with symptomatic myeloma diagnosed at the National Center for Cancer Care and Research in Qatar between 2007 and 2021 were included. Data on demographics, laboratory work, bone marrow analysis, radiology, and given treatment were collected. Descriptive statistics, survival curves, and multivariable cox regression were used to identify independent mortality risk factors. Results: During the study period of 15 years, a total of 192 patients were diagnosed with MM. The incident rate of myeloma cases in 2021 was 8 patients per million. The median age of patients was 57 years [range 22-88], with 68% being above the age of 50 years at diagnosis. The majority of patients were male (71%) and (85%) were expats. At the time of diagnosis, most patients [n = 169 (88%)] had bone lesions, and 27% had extramedullary plasmacytoma. Anemia, hypercalcemia, and spinal cord compression were reported in 53%, 28%, and 7% of patients, respectively, at presentation. The monoclonal immunoglobulin subtypes were IgG, IgA, and free light chain in 52%, 16%, and 26% of patients, respectively. The overall median survival was 103 months (95% CI 71-135 months). In a multivariate cox-regression analysis for risk factors, only high serum calcium (≥ 2.7 mmol/L) was associated with increased mortality (HR: 2.54, 95% C.I.: 1.40-4.63, p = 0.002). Patients who received an autologous stem cell transplant (ASCT) had significantly better overall survival. Conclusion: In this comprehensive study of patients with MM treated in a country with a small and young general population, centralized hematology care, and free cancer care, we found a low but increasing incidence of MM and a good overall survival. Hypercalcemia was confirmed as a negative risk factor. ASCT had a significant positive impact on survival and should be provided to all patients eligible for this treatment, even in the era of novel agents.

Early predictors of intensive care unit admission among COVID-19 patients in Qatar.

Background: COVID-19 is associated with significant morbidity and mortality. This study aimed to explore the early predictors of intensive care unit (ICU) admission among patients with COVID-19. Methods: This was a case-control study of adult patients with confirmed COVID-19. Cases were defined as patients admitted to ICU during the period February 29-May 29, 2020. For each case enrolled, one control was matched by age and gender. Results: A total of 1,560 patients with confirmed COVID-19 were included. Each group included 780 patients with a predominant male gender (89.7%) and a median age of 49 years (interquartile range = 18). Predictors independently associated with ICU admission were cardiovascular disease (adjusted odds ratio (aOR) = 1.64, 95% confidence interval (CI): 1.16-2.32, p = 0.005), diabetes (aOR = 1.52, 95% CI: 1.08-2.13, p = 0.016), obesity (aOR = 1.46, 95% CI: 1.03-2.08, p = 0.034), lymphopenia (aOR = 2.69, 95% CI: 1.80-4.02, p < 0.001), high AST (aOR = 2.59, 95% CI: 1.53-4.36, p < 0.001), high ferritin (aOR = 1.96, 95% CI: 1.40-2.74, p < 0.001), high CRP (aOR = 4.09, 95% CI: 2.81-5.96, p < 0.001), and dyspnea (aOR = 2.50, 95% CI: 1.77-3.54, p < 0.001). Conclusion: Having cardiovascular disease, diabetes, obesity, lymphopenia, dyspnea, and increased AST, ferritin, and CRP were independent predictors for ICU admission in patients with COVID-19.

Tyrosine Kinase Inhibitors in pediatric chronic myeloid leukemia: a focused review of clinical trials.

Tyrosine Kinase Inhibitors (TKIs) is revolutionizing the management of pediatric Chronic Myeloid Leukemia (CML), offering alternatives to Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT). We conducted a comprehensive review of 16 Randomized Controlled Trials (RCTs) encompassing 887 pediatric CML patients treated with TKIs including Imatinib, Dasatinib, and Nilotinib. The median patient age ranged from 6.5 to 14 years, with a median white blood cell count of 234 x 10^9/uL, median hemoglobin level of 9.05 g/dL, and median platelet count of 431.5 x 10^9/µL. Imatinib seems to be predominant first line TKI, with the most extensive safety and efficacy data. BCR::ABL response rates below 10% ranged from 60% to 78%, CCyR at 24 months ranged from 62% to 94%, and PFS showed variability from 56.8% to 100%, albeit with differing analysis timepoints. The Safety profile of TKIs was consistent with the known safety profile in adults. With the availability of three TKIs as first line options, multiple factors should be considered when selecting first line TKI, including drug formulation, administration, comorbidities, and financial issues. Careful monitoring of adverse events, especially in growing children, should be considered in long term follow-up clinical trials.

The Impact of Ethnicity on the Response to Eltrombopag in Patients With Immune Thrombocytopenia (ITP) in Qatar: A Single Institution Experience.

BACKGROUND: Eltrombopag olamine (ELT) is a synthetic nonpeptide with a low molecular weight that has been investigated in various phase-3 studies and shown to be efficacious at a typical dose of 50 mg. Varied ethnic groups have reported different responses to ELT. AIM: The aim is to examine the efficacy of ELT in Asian and Arab patients with immune thrombocytopenia (ITP) from the Indian subcontinent by starting with (12.5 mg, as a minimum dose) and gradually increasing to a maximum dose of 50 mg. METHODS: Between January 2015 and January 2019, we reviewed the electronic health records of non-Arab Asian (n = 17) versus Arab (n = 41) patients who were ≥18 years old, residing in Qatar, and with confirmed diagnoses with chronic ITP and under active treatment with a platelet count of 30,000/L, and bleeding symptoms. Following receiving ELT for three months or longer at various dosages, patients' response was examined. RESULTS: After three months of ELT therapy, the response rate (platelet count of 50,000/L) was equivalent in non-Arab (88.2%) versus Arab (87.5%) patients. However, to achieve an adequate response, 26% of Arab patients required a lower dose of 12.5 or 25 mg, and 41.5% required a higher dose of 50 mg. CONCLUSION:  In adult chronic ITP patients, ELT is typically well-tolerated and delivers the desired outcomes. In 67.5% of Arab patients, smaller dosages of ELT (12.5-50 mg) were helpful in sustaining acceptable PLT levels. This helps patients get the most benefit at the lowest feasible dose, reducing toxicity and expense.

Outcome of Pregnancy in the Era of PEGylated Interferon-α2a in Females with Chronic Myeloid Leukemia: An Experience from Qatar.

Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a myeloproliferative neoplasm characterized by increased proliferation of the granulocytic cell line without loss of its capacity to differentiate. It accounts for 20% of all adults affected by leukemia. Tyrosine kinase inhibitors revolutionized the treatment for CML and improved quality of life. Fertility is an important issue for both males and females. Here, we report our experience with a pregnant female with CML, and shed light on safety and efficacy of PEGylated interferon-αa in pregnant women with CML and its outcome.

Outcome of Pregnancy in the Era of Pegylated Interferon Alpha 2a in Females with Essential Thrombocythemia: An Experience from Qatar.

Myeloproliferative neoplasms are a diversified group of diseases of the hematopoietic stem cell, such as essential thrombocythemia (ET) and polycythemia vera. They are mainly caused by mutations in the following genes: JAK2, CALR, and MPL. All carry an increased risk to transform into acute leukemia or chronic myelogenous leukemia along with thrombosis and hemorrhagic complications. Treatment of such disorders during pregnancy is a challenging footstep, given the high risk of complications for both the mother and the fetus. Here, we report about two pregnant females with ET that has been treated with pegylated interferon alpha with safe and effective outcome.

Is Adherence to Imatinib Mesylate Treatment Among Patients with Chronic Myeloid Leukemia Associated with Better Clinical Outcomes in Qatar?

BACKGROUND: Despite the revolutionary success of introducing tyrosine kinase inhibitors (TKIs), such as imatinib mesylate (IM), for treating chronic myeloid leukemia (CML), a substantial proportion of patients' treatments fail. AIM: This study investigates the correlation between patient adherence and failure of TKIs' treatment in a follow-up study. METHODS: This is a follow-up study of a new cohort of CML patients. Adherence to IM is assessed using the Medication Event Monitoring System (MEMS 6 TrackCap, AARDEX Ltd). The 9-item Morisky Medication Adherence Scale, medication possession ratio (MPR) calculation, and the electronic medical records are used for identifying potential factors that influence adherence. Clinical outcomes are assessed according to the European Leukemia Net 2013 guidelines via reverse transcriptase quantitative polymerase chain reaction measurement of the level of BCR-ABL1 transcripts in peripheral blood. Response is classified at the hematological, cytogenetic, and molecular levels into optimal, suboptimal, or failure. RESULTS: A total of 36 CML patients (5 citizens and 31 noncitizen residents) consented to participate in the study. The overall mean MEMS score was 89. Of the 36 patients, 22 (61%) were classified as adherent (mean: 95) and 14 (39%) were classified as nonadherent (mean: 80.2). Adherent patients were significantly more likely to obtain optimal response (95%) compared to the nonadherent group (14.3%; P < 0.0001). The rate of poor adherence was as high as 39% using MEMS, which correlates with 37% treatment failure rate. The survey results show that 97% of patients increased the IM dose by themselves when they felt unwell and 31% of them took the missing IM dose when they remembered. Other factors known to influence adherence show that half of patients developed one or more side effects, 65% of patients experienced lack of funds, 13% of patients declared unavailability of the drug in the NCCCR pharmacy, and 72% of patients believed that IM would cure the disease. The MPR results reveal that 16% of patients had poor access to treatment through the hospital pharmacy. DISCUSSION AND CONCLUSION: This is the first prospective study to evaluate CML patients' adherence and response to IM in Qatar. The high rate of treatment failure observed in Qatar is explained by poor adherence. An economic factor (unaffordable drug prices) is one of the main causes of nonadherence and efforts should be made locally to improve access to medication for cancer diseases. Other risk factors associated with poor adherence could be improved by close monitoring and dose adjustment. Monitoring risk factors for poor adherence and patient education that include direct communication between the health-care teams, doctors, nurses, pharmacists, and patients are essential components for maximizing the benefits of TKI therapy and could rectify this problem. The preliminary results show that patients' response to treatment may be directly linked to patients' adherence to treatment. However, further in-depth and specific analysis may be necessary in a larger cohort.