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.

Chronic Myeloid Leukemia in Adolescents and Young Adults: Clinicopathological Variables and Outcomes.

INTRODUCTION: Adolescents and young adults (AYAs) diagnosed with chronic myeloid leukemia (CML) constitute a significant demographic group, particularly in regions with youthful populations like Qatar. Despite the global median age of CML diagnosis being 65 years, Qatar's age distribution reflects a younger cohort. This study investigates whether AYAs with CML exhibit distinct clinicopathological characteristics or outcomes compared to older age groups. METHODS: A total of 224 CML patients were enrolled, including 114 AYAs (defined as ages 15 through 39). Demographic and clinical parameters, including gender, BMI, BCR-ABL1 transcript type, white blood cell (WBC) count, hemoglobin level, platelet count, and spleen size, were compared between AYAs and older patients. Prognostic scoring systems (Sokal, Hasford, EUTOS, and ELTS) and molecular response rates (MMR and DMR) were also evaluated. RESULTS: AYAs demonstrated higher WBC counts at diagnosis (median 142.3 vs. 120; p = 0.037) and lower hemoglobin levels (10.5 vs. 11.40; p = 0.004) compared to older patients. Spleen size was significantly larger in AYAs (18.8 vs. 15.5; p = 0.001). While AYAs showed better prognostic scores by Sokal and Hasford criteria, EUTOS and ELTS scores indicated comparable risk stratification. However, AYAs exhibited lower rates of MMR (56.7% vs. 73.4%; p = 0.016) and achieved MMR at a slower pace (median time 130 vs. 103 months; p = 0.064). Similarly, the percentage of DMR was lower in AYAs (37.1% vs. 46.8%; p = 0.175). CONCLUSION: Despite their younger age, AYAs with CML displayed poorer prognoses compared to older patients. These findings underscore the importance of tailored management strategies for AYAs with CML to optimize outcomes in this distinct patient population.

Viral Infections and Incidence of Reactivations in Chronic Myeloid Leukemia Patients.

BACKGROUND: Viral infections remain a significant problem for patients with chronic myeloid leukemia (CML) who undergo stem cell transplants (SCTs). These infections often result from the reactivation of latent viruses. However, our understanding of the risk of viral reactivation in CML patients who have not undergone SCT is limited, and there is a scarcity of data on this topic. Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML as it is highly successful and has transformed the prognosis of patients with CML. However, TKI may be associated with an increased risk of infections. SUMMARY: We have performed a literature search for publications related to viral infections and their reactivations in patients with CML using PubMed, Scopus, and Google Scholar for the period 2001-2022. The population consisted of patients over 18 years old with a diagnosis of CML and no history of bone marrow transplantation. In an analysis of 41 patients, with 25 males and 16 females, M:F ratio of 1.56:1, and a median age of 50. Age ranged from 22 to 79 years. Most patients with reported viral infections or reactivations were in the chronic phase (CP) of CML, with 22 patients (76%) in the CP, 6 patients (21%) in the accelerated phase, and 1 patient (3%) in the blast phase. Most cases with reported outcomes responded to treatment for CML; only one had refractory disease and 8 cases (32%) had major molecular response. Imatinib was the most used TKI in 31 patients (77%). The most reported viral reactivations were herpes zoster in 17 cases (41%), followed by hepatitis B reactivation in 15 cases (37%). KEY MESSAGES: This review sheds light on the importance of having a hepatitis B serology checked before starting TKI therapy and close monitoring for viral infections and reactivations in patients with CML.

Pediatric Philadelphia-Negative Myeloproliferative Neoplasms in the Era of WHO Classification: A Systematic Review.

BACKGROUND: Philadelphia-negative myeloproliferative neoplasms (MPN) are most prevalent in the older population (median age at the diagnosis is above 60 years) and rarely diagnosed in pediatrics. Thus, our knowledge about the clinical presentation, mutational status, and complications of MPNs in pediatrics is limited. METHODS: The literature in English (PubMed, SCOPUS, and Google Scholar) was searched for studies, reviews, case series, and case reports of patients with Philadelphia-negative MPNs (including essential thrombocythemia, polycythemia vera, primary myelofibrosis, and profibrotic myelofibrosis) in the pediatrics age group (less than 18 years). Only studies that fulfilled WHO 2008 or 2016 criteria for MPNs were included. We aimed to describe the clinical characteristics, vascular and long-term complications, types of driver mutations, and treatment approaches in pediatric patients with MPNs. RESULTS: We reviewed 33 articles of available published literature from 2008 to 2022 and collected data from a total of 196 patients of the pediatric population. Among the cohort of patients, 139 had essential thrombocythemia (ET), 20 had polycythemia vera (PV), and 37 had primary myelofibrosis (PMF). The median age at the time of diagnosis for each disease varied, with 8.8 years for ET, 10 years for PV, and 3.6 years for MF. There was a slight difference in gender prevalence between both gender groups and all three diseases. The presenting symptoms were not mentioned in more than 50% of studies. We found that JAK2 was the most prevalent among all mutations. Both bleeding and thrombosis were present equally in ET, with 9% of cases complicated by bleeding and 9% complicated by thrombosis. Hemorrhagic events did not occur in patients with PV; thrombosis in children with MF was also not found. The progression into AML occurred in two patients with PV and one with ET. CONCLUSION: Given the rarity of MPNs in pediatrics and their different characteristics compared with adults, we believe there is a need for unique diagnostic criteria to match the different molecular statuses in pediatrics. Based on our review, the incidence of MPN complications in pediatrics, including thrombotic events, hemorrhage, and leukemic transformation, differs from that in adults.

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.

Prevalence of neutropenia among adult Arabs in Qatar: Relation to other hematological parameters and anthropometric data.

Neutropenia ranges from a normal variant to life-threatening acquired and congenital disorders. This study aims at providing baseline information regarding the prevalence and spectrum of neutropenia in the Arab blood donors who are living in Qatar. This retrospective cohort study was conducted to review the data of healthy Arab individuals (≥18 years) who donated blood between January 1, 2015 to May 15, 2019. A complete blood count was performed using automated analyzers. The prevalence of neutropenia was 10.7%. The prevalence in females was 32% and in males, it was 6%. Absolute neutrophil count (ANC) below 1 × 109/L was detected in 10% of Arab females and 1.8 % of Arab males. In females, the neutropenic group had significantly lower hemoglobin (Hb) levels and higher red cell distribution width, and lower total white blood cells and lymphocyte counts (P < .001) compared to the group with ANC > 1.5 × 109/L. Significant correlations were found between the ANC and Hb (r = 0.33, P < .05) and ANC and total white blood cells (r = 0.45, P < .01). The prevalence of neutropenia is considerably high in Arab adult females compared to other ethnic groups. Besides the genetic constitution of Arabs, the lower Hb and higher red cell distribution width in females suggest that iron deficiency could contribute to the development of neutropenia.

Hematological indices reference intervals for a healthy Arab population in Qatar: Effect of age, gender, and geographic location.

ABSTRACT: Hematologic reference intervals vary with gender, age, ethnicity, and geographic area. Therefore, local or national laboratory reference ranges are essential to enhance the accuracy when diagnosing health conditions. Still, no comprehensive list of reference ranges tailored to the Arab population living in Qatar. Accordingly, this study aims at establishing a hematology reference guide for Arabs in Qatar.This is a retrospective study where 750 healthy volunteers (18-69 years) from 2015 to 2019 were included, analyzed by an automated hematology analyzer. Arab adults were divided into African (Egypt, Libya, Tunisia, Morocco) and Asian (Syria, Lebanon, Jordon, Palestine, Qatar). The Cell-Dyn and Sysmex were used for measuring hematological parameters.The mean +/- 2SD were established for all the study groups. Arab males had significantly higher Hb, Hct, red cell distribution width, absolute neutrophil count, lymphocytes, and monocyte counts than females. Asian-Arab males had significantly higher Hb concentration and higher WBC, lymphocytes, and eosinophils than African Arabs. Asian-Arab young (>18: < 40 years) males had significantly higher Hb and lymphocytes and lower monocytes than older males (>40 years). African-Arab young males had significantly higher lymphocytes and lower monocytes than older males. Asian-Arab young females had higher WBC and absolute neutrophil count than older Asian Arabs.The findings of this study will help in establishing specific reference intervals in the Arab world. The differences in hematology reference intervals considering age, gender, and geographical location highlight the importance of establishing blood reference intervals in each country considering the ethnic diversity of each country.

Clinicopathological Variables and Outcome in Chronic Myeloid Leukemia Associated With BCR-ABL1 Transcript Type and Body Weight: An Outcome of European LeukemiaNet Project.

OBJECTIVE: It is debatable whether BCR-ABL1 transcript type has an impact on outcome of treatment of patients with CML, and it is not widely studied whether body weight influences response to treatment. In this study, we tried to find out if any of these factors has an impact on response to treatment and outcome. METHODOLOGY: We conducted a retrospective analysis of the files of 79 patients being treated in our center for CML with known BCR-ABL1 breakpoints, and patients' management and response assessment was done based on ELN 2013 guidelines. The analysis was performed based on two main groups, obese vs. normal BMI, and then based on BCR-ABL1 transcripts: e13a2 vs. e14a2. Cumulative incidence of MMR, CCyR, and DMR were estimated using the Kaplan-Meier survival curve method, and comparisons between groups were performed by the Log-rank/Gray test methods. RESULTS/CONCLUSION: In the patient-cohort studied, there was no statistically significant difference in molecular response between patients with CML based on body weight or transcript type although patients in the obesity group achieved higher and faster MMR with no statistical significance.

Efficacy and cost effectiveness of intravenous ferric carboxymaltose versus iron sucrose in adult patients with iron deficiency anaemia.

BACKGROUND: Iron deficiency anaemia (IDA) is a major health issues and common type of nutritional deficiency worldwide. For IDA treatment, intravenous (IV) iron is a useful therapy. OBJECTIVE: To determine the efficacy and cost-effectiveness (CE) of intravenous (IV) Ferric Carboxymaltose (FCM) versus IV Iron Sucrose (IS) in treating IDA. DATA SOURCES: Electronic medical record i.e. Cerner® system. TARGET POPULATION: Adults patients with iron deficiency anaemia. TIME HORIZON: A 12-month period (01/01/2018-31/12/2018). PERSPECTIVE: Hamad Medical Corporation (HMC, a public hospital). INTERVENTION: IV Ferric Carboxymaltose versus IV Iron Sucrose. OUTCOME MEASURES: With regard to responses to treatment i.e., efficacy of treatment with FCM & IS in IDA patients, hemoglobin (Hgb), ferritin, and transferrin saturation (TSAT) levels were the primary outcomes. Additionally, the researchers also collected levels of iron, platelet, white blood cell (WBC), red blood cell (RBC), mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV). The costs i.e. resources consumed (obtained from NCCCR-HMC) and the CE of FCM versus IS were the secondary outcomes. RESULTS OF BASE-CASE ANALYSIS: There was a significant improvement in Hgb, RBC and MCH levels in the IS group than the FCM group. The overall cost of IS therapy was significantly higher than FCM. The medication cost for FCM was approximately 6.5 times higher than IS, nonetheless, it is cheaper in terms of bed cost and nursing cost. The cost effectiveness (CE) ratio illustrated that FCM and IS were significantly different in terms of Hgb, ferritin and MCH levels. Further, Incremental Cost Effectiveness Ratio (ICER) indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes. RESULTS OF SENSITIVITY ANALYSIS: Not applicable. LIMITATIONS: The study did not consider the clinical or humanistic outcome. CONCLUSIONS: The higher cost of FCM versus IS can be offset by savings in healthcare personnel time and bed space. ICER indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes.

Leukemia Cutis as an Early Presentation or Relapsing Manifestation of Chronic Lymphocytic Leukemia (CLL).

BACKGROUND AND OBJECTIVE: Cutaneous infiltration by Chronic Lymphocytic Leukemia (CLL) is a rare complication. The clinical presentation, impact of it on disease prognosis, and the proper treatment choice are not clear. Here in our review, we try to answer these questions. Acquisition of evidences: A systematic search of PubMed, and Google Scholar for English language articles published from Jan 2000 to June 2019. Synthesis of evidences: A total of 56 cases were identified, with a median age of 66 years. Of these cases 43 were males and 12 were females, and one missing data, with a ratio of 3,6:1. Head and neck were most commonly involved. The commonest clinical presentation was papulonodular lesions, and the majority were diagnosed at an early stage. CLL skin involvement at the site of old herpetic lesions was common. Because of the rarity of the disease, treatment modalities varied widely, and there are no consensus on treatment. The majority were treated with chemotherapy. In general, 35 (77.8% - of the non-missing data) patients responded to treatment (25 patients had a complete remission and 10 a partial remission). All patients ≤60 years had an early-stage disease, on the other hand, all patients with advanced-stage were >60 years. CONCLUSION: Patients with early-stage and localized leukemia cutis can benefit from observation alone strategy, while intervention in young patients with advanced disease is warranted. Skin infiltration by CLL does not affect prognosis, as most patients attained complete or partial remission with a very low progression rate.

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.

Subcutaneous Masses as an Unusual Manifestation of Relapse in a Case of Atypical Chronic Lymphocytic Leukemia with Prolymphocytoid Transformation and Complex Karyotype: A Diagnostic Dilemma and Treatment Challenge.

BACKGROUND Most patients with chronic lymphocytic leukemia (CLL) are asymptomatic at diagnosis, but 10% present with B symptoms. Most patients have palpable lymphadenopathy, while 20-50% of the patients have hepatosplenomegaly. Cutaneous infiltrations in patients with CLL can be localized or generalized in the form of erythematous papules, plaques, nodules and, ulceration, which is uncommon. CASE REPORT We present the case of a 71-year-old man diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with atypical immunophenotype and increased prolymphocytes (CLL/PLL), which was treated initially after white blood counts (WBC) doubling with Bendamustine and Rituximab for 6 cycles, and achieved complete remission. The patient relapsed after 6 months of completion of treatment, with multiple large subcutaneous masses, proved to be infiltration with the same atypical CLL/SLL on tissue biopsy, with pathologic features indicating disease progression. The lack of similar reported cases, and the aggressiveness of the tumor clinically and histopathologically, resulted in the decision to treat with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone (R-CHOP) as a case of aggressive lymphoma, with complete remission clinically and radiologically. CONCLUSIONS We present a rare case of subcutaneous extramedullary masses of atypical CLL/SLL. The high proliferation index (Ki-67) and the increase of large cells are suggestive of aggressive progression of the disease; however, no frank features of Richter's transformation were noted. Based on this and because of the unusual aggressive-looking skin masses, the panel decided to treat the patient with R-CHOP. The impact of this presentation on the prognosis of the disease is not clear. To date, our patient has responded well to treatment with R-CHOP, with complete remission of the subcutaneous masses and on PET scan, but further follow-up is needed.

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.

A Rare Case of Hairy Cell Leukemia with Unusual Loss of CD123 Associated with COVID-19 at the Time of Presentation.

Coronavirus disease 2019 (COVID-19) pandemic has been a serious threat and has been reported with different presentations and complications. Older age, along with comorbidities such as diabetes, hypertension, or cardiac disease, increases the risk factors for COVID-19 severity and death [N Engl J Med. 2020;382(18):1708-20 and Lancet Respir Med. 2020 05;8(5):475-81]. It is proposed that cancer patients have a significantly higher incidence of severe incidents including admission to the intensive care unit, the necessity for assisted ventilation, and even death after catching the virus compared with non-cancer patients [Lancet Oncol. 2020;21(3):335-7]. It is also described that cancer patients appear to be twice as likely to contract infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [JAMA Oncol. 2020;6(7):1108-10]. Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder, with patients typically presenting with cytopenias, marked splenomegaly in 80-90% of patients, circulating leukemia cells, bone marrow infiltration and the presence of BRAF V600E somatic mutation [Indian J Hematol Blood Transfus. 2014;30(Suppl 1):413-7]. Leukemic cells classically have central nuclei and abundant cytoplasm with hairy-like projections and express CD11c, CD25, CD103, and CD123 [Indian J Hematol Blood Transfus. 2014;30(Suppl 1):413-7]. Loss of CD123 in HCL has been rarely reported in the literature [Am J Hematol. 2019;94(12):1413-22]. We describe a unique case of a COVID-19-positive male who presented with severe respiratory symptoms, deteriorated quickly, and was intubated. Workup of severe progressive pancytopenia and bone marrow examination revealed HCL without splenomegaly and with atypical unusual loss of CD123. To our knowledge, this is the first case of CD123-negative HCL without splenomegaly associated with COVID-19 infection as the initial presentation.