Hematology/oncology And Stem Cell Therapy[JOURNAL]
Sun
200 papers
The Hispanic Paradox in Non-Small Cell Lung Cancer.
Kumar R, Castillero F, Bhandari S … +2 more , Malapati S, Kloecker G
Hematol Oncol Stem Cell Ther · 2022 Jun · PMID 33775613 · Publisher ↗
OBJECTIVE/BACKGROUND: According to the U.S. Census Bureau, 18% of the total population in the United States identified themselves as Hispanic in 2016 making it the largest minority group. This study aimed to evaluate the...
OBJECTIVE/BACKGROUND: According to the U.S. Census Bureau, 18% of the total population in the United States identified themselves as Hispanic in 2016 making it the largest minority group. This study aimed to evaluate the effect of Hispanic ethnicity on the overall survival of patients with non-small cell lung cancer (NSCLC) using a large national cancer database. METHODS: We used the National Cancer Database to identify patients diagnosed with NSCLC between 2010 and 2015. The two comparative groups for this study were non-Hispanic Whites (NHWs) and Hispanics. The primary outcome was overall survival. RESULTS: Of the 555,475 patients included in the study, 96.9% and 3.1% were NHWs and Hispanics with a median follow up of 12.6 months (interquartile range 4.1-30.6) and 12.1 months (interquartile range 3.8-29.5), respectively. Hispanics were more likely to be uninsured, and live in areas with lower median household income or education level. In the age-, sex-, and comorbidities-adjusted Cox model, the overall survival was significantly better in Hispanics compared with NHWs (hazard ratio [HR] 0.92, 95% confidence interval 0.90-0.93, p < .001). In a demographic, socioeconomic, clinical, and facility characteristics adjusted Cox model, Hispanics had further improvement in survival (HR 0.79, 95% confidence interval 0.78-0.81, p < .001). The survival advantage was seen in all cancer stages: Stage I-HR 0.76 (0.71-0.80), Stage II-HR 0.85 (0.79-0.92), Stage III-HR 0.81 (0.77-0.85), and Stage IV-HR 0.79 (0.77-0.81). CONCLUSION: Hispanic ethnicity was associated with better survival in NSCLC. This survival advantage is likely the result of complex interactions amongst several physical, social, cultural, genomic, and environmental factors.
Molecular mediators of breast cancer metastasis.
Yeeravalli R, Das A
Hematol Oncol Stem Cell Ther · 2021 Dec · PMID 33744312 · Publisher ↗
Breast cancer has the highest incidence rate of malignancy in women worldwide. A major clinical challenge faced by patients with breast cancer treated by conventional therapies is frequent relapse. This relapse has been...
Breast cancer has the highest incidence rate of malignancy in women worldwide. A major clinical challenge faced by patients with breast cancer treated by conventional therapies is frequent relapse. This relapse has been attributed to the cancer stem cell (CSC) population that resides within the tumor and possess stemness properties. Breast CSCs are generated when breast cancer cells undergo epithelial-mesenchymal transition resulting in aggressive, highly metastatic, and invasive phenotypes that exhibit resistance towards chemotherapeutics. Metastasis, a phenomenon that aids in the migration of breast CSCs, occurs through any of three different routes: hematogenous, lymphatic, and transcoelomic. Hematogenous dissemination of breast CSCs leads to metastasis towards distant unrelated organs like lungs, liver, bone, and brain causing secondary tumor generation. Activation of metastasis genes or silencing of metastasis suppressor genes often leads to the advancement of metastasis. This review focuses on various genes and molecular factors that have been implicated to regulate organ-specific breast cancer metastasis by defying the available therapeutic interventions.
Role of gene therapy in Fanconi anemia: A systematic and literature review with future directions.
Shafqat S, Tariq E, Parnes AD … +3 more , Dasouki MJ, Ahmed SO, Hashmi SK
Hematol Oncol Stem Cell Ther · 2021 Dec · PMID 33736979 · Publisher ↗
Gene therapy (GT) has been reported to improve bone marrow function in individuals with Fanconi anemia (FA); however, its clinical application is still in the initial stages. We conducted this systematic review, followin...
Gene therapy (GT) has been reported to improve bone marrow function in individuals with Fanconi anemia (FA); however, its clinical application is still in the initial stages. We conducted this systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to assess the long-term safety and clinical outcomes of GT in FA patients. Electronic searches from PubMed, Web of Science, Cochrane Library, and Google Scholar were conducted and full texts of articles meeting our inclusion criteria were reviewed. Three clinical trials were included, with a total of nine patients and mean age of 10.7 ± 5.7 years. All patients had lentiviral-mediated GT. A 1-year follow-up showed stabilization in blood lineages, without any serious adverse effects from GT. A metaregression analysis could not be conducted, as very little long-term follow-up data of patients was observed, and the median survival rate could not be calculated. Thus, we can conclude that GT seems to be a safe procedure in FA; however, further research needs to be conducted on the longitudinal clinical effects of GT in FA, for a better insight into its potential to become a standard form of treatment.
Subcutaneous immunoglobulin in allogeneic hematopoietic cell transplant patients: A prospective study of feasibility, safety, and healthcare resource use.
Pasic I, Alanazi W, Dranitsaris G … +5 more , Lieberman L, Viswabandya A, Kim DDH, Lipton JH, Michelis FV
Hematol Oncol Stem Cell Ther · 2021 Dec · PMID 33684377 · Publisher ↗
BACKGROUND: We evaluated feasibility, safety, and total resource use of subcutaneous immunoglobulin (SCIG) in a pilot study of patients who underwent allogeneic hematopoietic cell transplant (HCT) over a 6-month period....
BACKGROUND: We evaluated feasibility, safety, and total resource use of subcutaneous immunoglobulin (SCIG) in a pilot study of patients who underwent allogeneic hematopoietic cell transplant (HCT) over a 6-month period. METHODS: A total of 20 eligible patients were treated with SCIG at 0.1 g/kg/week for up to 6 months. Patients were matched to 20 concurrent intravenous immunoglobulin (IVIG) controls. Clinical outcomes measured included adverse reactions, healthcare resource use, patient satisfaction, and quality of life (QOL). (ClinicalTrials.gov Identifier: NCT03401268.) RESULTS: Groups were comparable in terms of age, weight, sex, transplant indication, donor type, and conditioning intensity. All 20 IVIG patients completed 6 consecutive months of therapy compared with 13/20 (65%) SCIG patients. There were no adverse reactions in IVIG patients, compared with six (30%) SCIG patients. All adverse reactions in SCIG patients were grade I, transient, and required no medical intervention. Median overall cost per patient was lower with SCIG than with IVIG ($9,756 vs. $13,780, p = .046). Among patients who completed 6 months of SCIG, median preference and satisfaction scores were 100%. Over the 6-month period, QOL scores remained stable in SCIG patients. CONCLUSIONS: In a subgroup of patients, SCIG was associated with high patient satisfaction and a reduction in total healthcare costs compared with IVIG in a cohort of HCT patients.
A short review on DNA damage and repair effects in lip cancer.
Toprani SM, Kelkar Mane V
Hematol Oncol Stem Cell Ther · 2021 Dec · PMID 33626329 · Publisher ↗
Increasing trend in oral cancer (0.6% per year) and its related mortality has been reported worldwide since 2010. The United States alone reports an increase of 57% within the past 10 years. This emphasizes the need not...
Increasing trend in oral cancer (0.6% per year) and its related mortality has been reported worldwide since 2010. The United States alone reports an increase of 57% within the past 10 years. This emphasizes the need not only for designing strategies of prevention and planning but also for an effective treatment regime for the various oral cancers. Cancers of the lips, tongue, cheeks, floor of the mouth, and hard palate have been primarily classified under the category of oral cancers. If left undiagnosed, these cancers can be life threatening. Amongst these, the most undesignated and understudied cancer type is the lip carcinoma, which is either categorized under oral cancer or/as well as skin cancer or head and neck cancer. However, lip cancer corresponds to 25-30% of all diagnosed oral cancers. Though the etiology of lip cancer is not yet fully understood, numerous risk factors involved in its development are now being studied. The cells in the lip region are continuously exposed to various DNA damaging agents from endogenous as well as exogenous sources. Flaws in DNA repair mechanisms involved in eliminating these damages may be linked to the origin of carcinogenesis. Accumulation of DNA damage and defect in repair mechanisms may play a role in lip carcinogenesis and progression. This literature review is an exhaustive compilation of the research work performed on the role of DNA damage and repair responses in lip carcinoma which will pave a path for researchers to identify predictive DNA repair biomarker/s for lip cancer, and its diagnosis, prevention, and treatment.
Stem Cell-Based Therapies and Glioblastoma: A Seminal Matter.
Kumaria A
Hematol Oncol Stem Cell Ther · 2022 Mar · PMID 33617791 · Publisher ↗
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Does Race Play a Role in Complications and Outcomes of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms?
Peseski AM, Saliba AN, Althouse SK … +1 more , Sayar H
Hematol Oncol Stem Cell Ther · 2022 Jun · PMID 33607101 · Publisher ↗
BACKGROUND: Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of hematologic malignancies with known vascular complications. The role race and ethnicity play in these complications is less d...
BACKGROUND: Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a group of hematologic malignancies with known vascular complications. The role race and ethnicity play in these complications is less defined. We aimed to further evaluate the role of race in patients without a history of previous thrombotic or hemorrhagic events. METHODS: In this retrospective study, 300 adult patients with MPN were included; 270 (90.0%) were White and 30 (10.0%) were non-White. The non-White group primarily consisted of African American or Black (26 patients), followed by others. Median age at diagnosis was 58 years for White patients and 61.5 years for non-White patients. The interaction between outcomes and vascular events with race was evaluated using multivariate logistical regression models. RESULTS: The incidence of thrombotic events was inversely correlated with age at diagnosis, with younger patients demonstrating a higher rate of thrombotic events over time (p < .001). The incidence of thrombotic or hemorrhagic events did not differ between White and non-White patients. A statistically significant difference in median survival was observed between White and non-White patients: 29 years (95% confidence interval [CI]: 21.8-not reached) versus 13 years (95% CI: 5.7-22.7), respectively (p=.016). CONCLUSION: This study did not find a significant difference in the rate of thrombotic or hemorrhagic events between White and non-White patients with MPN but suggested that non-White patients had significantly shorter median survival than White patients. Such observations may inform future studies to further characterize racial disparities in outcomes.
A Novel Frameshift Mutation in the ITGB3 Gene Leading to Glanzmann's Thrombasthenia in a Saudi Arabian Family.
Alharbi A, Hashmi JA, Alharby E … +3 more , Albalawi AM, Ramzan K, Basit S
Hematol Oncol Stem Cell Ther · 2022 Mar · PMID 33600779 · Publisher ↗
Glanzmann's thrombasthenia (GT) is an autosomal recessive congenital bleeding disorder of platelet aggregation. Mutations in ITGA2B and ITGB3 genes result in quantitative and/or qualitative abnormalities of the glycoprot...
Glanzmann's thrombasthenia (GT) is an autosomal recessive congenital bleeding disorder of platelet aggregation. Mutations in ITGA2B and ITGB3 genes result in quantitative and/or qualitative abnormalities of the glycoprotein receptor complex IIb/IIIa (integrin αIIbβ3), which in turn impairs platelet aggregation and lead to GT. In this study, whole genome single nucleotide polymorphism (SNP) genotyping as well as whole exome sequencing was performed in a large family segregating GT. Analysis of the genotypes localized the disease region to chromosome 17q21.2-q21.3. Filtration of whole exome data and candidate variants prioritization identified a pathogenic variant in the ITGB3 gene. The single nucleotide deletion variant (c.2113delC) in exon 13 of the ITGB3 gene is predicted to cause a frameshift and absence of vital C-terminal domains including the transmembrane helix and the cytoplasmic domain. Clinical variability of the bleeding phenotype in affected individuals with the same mutation suggests that other genetic and nongenetic factors are responsible for determining GT features.
Prevalence and Distribution of Major β-Thalassemia Mutations and HbE/β-Thalassemia Variant in Nepalese Ethnic Groups.
Lama R, Yusof W, Shrestha TR … +4 more , Hanafi S, Bhattarai M, Hassan R, Zilfalil BA
Hematol Oncol Stem Cell Ther · 2022 Mar · PMID 33592169 · Publisher ↗
BACKGROUND: Beta-thalassemia is a genetic disorder that is inherited in an autosomal recessive pattern. This genetic disease leads to a defective beta-globin hemoglobin chain causing partial or complete beta-globin chain...
BACKGROUND: Beta-thalassemia is a genetic disorder that is inherited in an autosomal recessive pattern. This genetic disease leads to a defective beta-globin hemoglobin chain causing partial or complete beta-globin chain synthesis loss. Beta-thalassemia major patients need a continuous blood transfusion and iron chelation to maintain the normal homeostasis of red blood cells (RBCs) and other systems in the body. Patients also require treatment procedures that are costly and tedious, resulting in a serious health burden for developing nations such as Nepal. METHODS: A total of 61 individuals clinically diagnosed to have thalassemia were genotyped with multiplex amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Twenty-one major mutations were investigated using allele-specific primers grouped into six different panels. RESULTS: The most common mutations found (23%) were IVS 1-5 (G-C) and Cd 26 (G-A) (HbE), followed by 619 deletion, Cd 8/9 (+G), Cd 16 (-C), Cd 41/42 (-TTCT), IVS 1-1 (G-T), Cd 19 (A-G), and Cd 17 (A-T) at 20%, 12%, 8%, 6%, 4%, 3%, and 1%, respectively. CONCLUSION: The results of this study revealed that Nepal's mutational profile is comparable to that of its neighboring countries, such as India and Myanmar. This study also showed that thalassemia could be detected across 17 Nepal's ethnic groups, especially those whose ancestors originated from India and Central Asia.
COVID-19-positive cancer patients undergoing active anticancer treatment: An analysis of clinical features and outcomes.
Ali J, Sajjad K, Farooqi AR … +3 more , Aziz MT, Rahat A, Khan S
Hematol Oncol Stem Cell Ther · 2021 Dec · PMID 33387453 · Full text
BACKGROUND: Cancer patients, particularly those on active anticancer treatment, are reportedly at a high risk of severe coronavirus disease 2019 (COVID-19) infection and death. This study aimed to describe the clinical c...
BACKGROUND: Cancer patients, particularly those on active anticancer treatment, are reportedly at a high risk of severe coronavirus disease 2019 (COVID-19) infection and death. This study aimed to describe the clinical characteristics and outcomes of patients diagnosed with COVID-19 whilst on anticancer treatment in a developing country. METHODS: This is a retrospective observational study of all adult cancer patients at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Pakistan, from March 15, 2020 to July 10, 2020, diagnosed with COVID-19 within 4 weeks of receiving anticancer treatment, where a purposive sampling was performed. Cancer patients who did not receive anticancer treatment and clinical or radiological diagnosis of COVID-19 without a positive reverse transcription-polymerase chain reaction (RT-PCR) test were excluded. The primary endpoint was all-cause mortality after 30 days of COVID-19 test. Data was analyzed with SPSS version 23 (SPSS Inc., Chicago, IL, USA). Categorical parameters were computed using chi-square test, keeping p value < 0.05 as significant. RESULTS: A total of 201 cancer patients with COVID-19 were analyzed. The median age of patients was 45 (18-78) years. Mild symptoms were present in 162 (80.6%) patients, whereas severe symptoms were present in 39 (19.4%) patients. The risk of death was statistically significant (p < .05) amongst patients with age greater than 50 years, metastatic disease, and ongoing palliative anticancer treatment. Anticancer treatment (chemotherapy, radiotherapy, hormonal therapy, targeted therapy, and surgery) received within preceding 4 weeks had no statistically significant (p > .05) impact on mortality. CONCLUSIONS: In cancer patients with COVID-19, mortality appears to be principally driven by age, advanced stage of the disease, and palliative intent of cancer treatment. We did not identify evidence that cancer patients on chemotherapy are at significant risk of mortality from COVID-19 correlating to those not on chemotherapy.
Dose-adjusted bendamustine as a replacement for carmustine in autologous stem cell transplant conditioning for patients with relapsed lymphoma: A retrospective single-center study.
AlJohani NI, Nasani M, Ahmed HE … +4 more , Ur Rehman J, Nawaz A, Alzahrani Z, Albeirouti B
Hematol Oncol Stem Cell Ther · 2021 Dec · PMID 33306964 · Publisher ↗
BEAM conditioning regimen (carmustine [BCNU], etoposide, cytarabine, and melphalan) has been widely used for autologous stem cell transplantation in patients with relapsed or refractory lymphoma. However, BCNU-associated...
BEAM conditioning regimen (carmustine [BCNU], etoposide, cytarabine, and melphalan) has been widely used for autologous stem cell transplantation in patients with relapsed or refractory lymphoma. However, BCNU-associated toxicities have prompted research to explore other options. This study aimed to assess the feasibility of bendamustine as an alternative to BCNU. We compared 71 patients who received either bendamustine (Benda-EAM group) or BCNU (BEAM group) conditioning. Considering previous reports of increased cardiotoxicity, nephrotoxicity, and mucositis, we adopted a lower bendamustine dose of 160 mg/m/day administered for 2 days. There was no increase in nephrotoxicity and cardiotoxicity. Further, positive results were also obtained for neutrophil and platelet engraftment, appearing earlier in patients treated with Benda-EAM (10 vs. 14 days and 16 vs. 27 days, respectively). However, caution is warranted because an increased frequency of Grade 3 mucositis was observed in the Benda-EAM group (82.4% vs. 48%). This was accompanied by an increased need for parenteral nutrition. Despite the lower dose of bendamustine, the overall and progression-free survival rates were comparable between the Benda-EAM and BEAM groups. In conclusion, a lower dose of bendamustine may be an attractive alternative to BCNU as a tolerable treatment modality for patients with relapsed/refractory lymphoma.
Survival following relapse after allogeneic hematopoietic cell transplantation for acute leukemia and myelodysplastic syndromes in the contemporary era.
Hong S, Rybicki L, Corrigan D … +10 more , Hamilton BK, Sobecks R, Kalaycio M, Gerds AT, Dean RM, Hill BT, Pohlman B, Jagadeesh D, Anwer F, Majhail NS
Hematol Oncol Stem Cell Ther · 2021 Dec · PMID 33301747 · Publisher ↗
OBJECTIVE/BACKGROUND: Relapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT). No standard of care exists, and a wide range of treatments are used for post-allo...
OBJECTIVE/BACKGROUND: Relapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT). No standard of care exists, and a wide range of treatments are used for post-alloHCT relapse. In the recent era, several novel therapies including targeted agents are available for acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS). METHODS: We reviewed outcomes after alloHCT relapse, with or without use of these newer agents for ALL, AML, and MDS. In total, 115 adults with relapsed or refractory ALL (n = 17), AML (n = 67), and MDS (n = 31) at median 5 (range, 1-64) months after their first alloHCT in 2010-2018 were included. RESULTS: Median follow-up was 19 (range, 6-80) months after relapse from alloHCT. Targeted agents were given to 29 (25%) patients. In multivariable analysis, use of targeted agent at any time point after relapse was not associated with survival. Matched unrelated (vs. matched sibling; hazard ratio [HR] 1.70; p = .027) or haploidentical donor grafts (vs. matched sibling; HR 2.69; p = .003), presence of grade II-IV acute graft-versus-host disease before relapse (HR 2.46; p < .001), and less than 12 months from HCT to relapse (<6 vs. > 12 months; HR 6.34; p < .001; 6-12 vs. > 12 months; HR 3.16; p = .005) were adverse prognostic factors for post-relapse survival. CONCLUSION: Outcomes after alloHCT relapse remain poor regardless of the novel agent use. Innovative treatment strategies are needed to improve outcomes after relapse post-alloHCT.
Profile of entrectinib in the treatment of ROS1-positive non-small cell lung cancer: Evidence to date.
Araujo JM, Gomez AC, Pinto JA … +2 more , Rolfo C, Raez LE
Hematol Oncol Stem Cell Ther · 2021 Sep · PMID 33290717 · Publisher ↗
ROS proto-oncogene 1 (ROS1) encodes a type I integral membrane protein with tyrosine kinase activity and whose activating alterations are involved in the aggressiveness of several tumor types. Fusions involving ROS1 gene...
ROS proto-oncogene 1 (ROS1) encodes a type I integral membrane protein with tyrosine kinase activity and whose activating alterations are involved in the aggressiveness of several tumor types. Fusions involving ROS1 gene are present in 1-2% of lung adenocarcinomas and other solid tumors. Entrectinib, also known as RXDX-101, is a potent second-generation, multitarget oral inhibitor against NTRK1, NTRK2, NTRK3, ALK, and ROS1 with the ability to cross the blood-brain barrier. Results of Phase I and II trials have led the Food and Drug Administration to grant approval to entrectinib for the treatment of patients with metastatic, ROS1-positive non-small cell lung cancer (NSCLC). In this review, we will describe the biology of ROS1, as well as results of the efficacy and safety of different clinical trials evaluating entrectinib in ROS1-positive NSCLC.
New promising developments for potential therapeutic applications of high-dose ascorbate as an anticancer drug.
Testa U, Pelosi E, Castelli G
Hematol Oncol Stem Cell Ther · 2021 Sep · PMID 33278349 · Publisher ↗
Vitamin C (ascorbate) is an essential dietary requirement, with fundamental redox, anti-oxidant functions at physiologic concentrations. Vitamin C is a cofactor for Fe and 2-oxoglutarate-dependent dioxygenases, englobing...
Vitamin C (ascorbate) is an essential dietary requirement, with fundamental redox, anti-oxidant functions at physiologic concentrations. Vitamin C is a cofactor for Fe and 2-oxoglutarate-dependent dioxygenases, englobing large families of enzymes, including also epigenetic regulators of DNA and histone methylation. Importantly, vitamin C is involved in the control of the activity of TET (ten-eleven translocation) enzymes, key epigenetic regulators. For this spectrum of activities, often involving pathways deregulated in cancer cells, vitamin C possesses some pharmacologic activities that can be exploited in anticancer therapy. In particular, the capacity of pharmacological doses of vitamin C to target redox imbalance and to rescue deregulated epigenetic program observed in some cancer cells represents a consistent therapeutic potentiality. Several recent studies have identified some cancer subsets that could benefit from the pharmacological activities of vitamin C. The identification of these potentially responsive patients will help to carefully define controlled clinical trials aiming to evaluate the anticancer activity of Vitamin C.
Prognostic factors for clinical outcomes of patients with central nervous system leukemia.
Bharucha J, Cao Q, Sachs Z … +8 more , Smith A, Williams S, Amin K, Bachanova V, Warlick E, Brunstein C, Weisdorf D, Bejanyan N
Hematol Oncol Stem Cell Ther · 2021 Sep · PMID 33271117 · Full text
Prognostic factors associated with clinical outcomes of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients with central nervous system (CNS) involvement are unknown. We retrospectively studied t...
Prognostic factors associated with clinical outcomes of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients with central nervous system (CNS) involvement are unknown. We retrospectively studied the characteristics and outcomes of 66 (18 pediatric and 48 adult) patients with CNS leukemia with ALL (n = 41) or AML (n = 25). The median age of patients at diagnosis of CNS leukemia was 30 (range, 1-69) years. Nearly two-third patients had CNS involvement at the initial diagnosis of leukemia. Complete remission of CNS leukemia was attained in 58 (88%) patients, and probability of overall survival at 36 months after the diagnosis of CNS leukemia was 43% for the entire cohort. We identified that achieving remission of systemic leukemia and having CNS leukemia diagnosed and treated before allogeneic transplantation were the factors associated with CNS leukemia remission. Prognostic factors associated with better overall survival in patients with CNS leukemia included pediatric age, diagnosis of CNS leukemia before receiving allogenic transplantation, achieving clearance of systemic or CNS leukemia, receiving no cranial radiation in conjunction with intrathecal chemotherapy (IT), and receiving IT consolidation after achieving remission of CNS leukemia. Our findings show that patients with CNS leukemia are at considerable risk of mortality. Awareness of modifiable prognostic factors such as avoidance of cranial radiation whenever possible and use of IT consolidation can result in improved outcomes in subset of patients with CNS leukemia.
Spectrum of Myelodysplastic Syndrome in Patients Evaluated for Cytopenia(s). A Report from a Reference Centre in Saudi Arabia.
AlMozain N, Mashi A, Alneami Q … +9 more , Al-Omran A, Bakshi N, Owaidah T, Khalil S, Khogeer H, Hashmi S, Al-Sweedan S, Morris T, AlNounou R
Hematol Oncol Stem Cell Ther · 2022 Jun · PMID 33227261 · Publisher ↗
BACKGROUND/OBJECTIVE: Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells, characterized by ineffective hematopoiesis, peripheral cytopenias along with hypercellularity of the bone marrow, and...
BACKGROUND/OBJECTIVE: Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells, characterized by ineffective hematopoiesis, peripheral cytopenias along with hypercellularity of the bone marrow, and marked dysplastic features. Establishing MDS diagnosis is difficult due to nonspecific clinical presentation and imprecise morphological criteria. In anticipation to improve the diagnostic approach in this field, we aimed to characterize the clinical and morphological features of patients presented with cytopenias with a special focus on MDS. METHODS: We comprehensively reviewed all medical record of patients who were referred to the hematology laboratory at KFSH-RC, Riyadh, Saudi Arabia, between January 2009 and March 2016 for evaluation of bone marrow aspirates and trephine biopsies due to severe and persistent cytopenia(s) to rule out MDS. RESULTS: A total of 183 patients, 155 adult and 28 pediatric, were identified. In the adult group, MDS was diagnosed in 82 (52.9%) patients, with a male-to-female (M:F) ratio of 1.6:1 and mean age at diagnosis of 50 years. According to the World Health Organization (WHO) 2017 criteria, MDS subtypes were as follows: MDS with single lineage dysplasia (SLD, 5%), MDS with ring sideroblasts and SLD (MDS-RS-SLD 7%), MDS with multilineage dysplasia (MDS-MLD 21%), MDS with deletion of chromosome 5q (MDS del(5q), 2%), MDS unclassifiable (MDS-U7%), hypoplastic MDS (h-MDS 4%), MDS with excess blasts-1 (MDS-EB1, 20%), MDS with excess blasts-2 (MDS-EB2, 28%), and therapy-related MDS (6%). Laboratory and morphological features were described. In both groups, cytogenetic abnormalities were classified according to the Revised International Prognostic Scoring System cytogenetic risk groups. In adults, the dominating cytogenetic abnormalities were monosomy 5 and monosomy 7 seen in 20.7% and 24.4% of patients, respectively. Peripheral cytopenia not due to MDS was diagnosed in 54 (34.8%) patients, with a mean age of 43 years and M:F ratio of 1:1. The cause of these cytopenias were as follows: bone marrow failure (BMF, 22%), peripheral destruction (20%), drug induced (20%), anemia of chronic disease (16%), B12 deficiency (7%), infection (7%), paroxysmal nocturnal hemoglobinuria (4%), idiopathic cytopenia of undetermined significance (2%), and idiopathic dysplasia of undetermined significance (2%). A definite diagnosis of MDS was not possible in 19 patients due to insufficient clinical data. In the pediatric group, MDS was diagnosed in 14/28 (50%) patients, with M:F ratio of 1.8:1 and mean age at diagnosis of 4 years. MDS subtypes (WHO 2017) in 14 patients were as follows: refractory cytopenia of childhood (RCC, 42.8%), MDS-EB1 (42.8%), and MDS-EB2 (14.2%). Laboratory and morphological features were described. The prevalent cytogenetic abnormality was monosomy 7 in six/14 (42.8%) patients. Cytopenias due to other causes were diagnosed in eight/28 patients (28.5%), with a mean age of 6.5 years and M:F ratio of 1.6:1. The causes of non-MDS related cytopenia were: congenital BMF (4 patients), peripheral destruction (2 patients), immune deficiency (1 patient), and viral infection (1 patient). A definite diagnosis of MDS could not be made in six/28 (21.4%) patients. CONCLUSION: MDS is the cause of cytopenia in a significant number of patients referred for evaluation of cytopenias, appears at younger age, and tends to be more aggressive than that reported in international studies. Anemia, dysplastic neutrophils in the peripheral blood, and dysplastic megakaryocytes in the bone marrow trephine biopsy are the most reliable features in distinguishing MDS from other alternative diagnoses.
Frequency of MYD88 L256P mutation and its correlation with clinico-hematological profile in mature B-cell neoplasm.
Shekhar R, Naseem S, Binota J … +2 more , Varma N, Malhotra P
Hematol Oncol Stem Cell Ther · 2021 Sep · PMID 33217360 · Publisher ↗
OBJECTIVE/BACKGROUND: B-cell neoplasms are clonal tumors of B cells at various stages of maturation, including diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic lymphoma (CLL), Burkitt lymphoma (BL), lymphoplasm...
OBJECTIVE/BACKGROUND: B-cell neoplasms are clonal tumors of B cells at various stages of maturation, including diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic lymphoma (CLL), Burkitt lymphoma (BL), lymphoplasmacytic lymphoma (LPL)/Waldenström's macroglobulinemia (WM), splenic marginal zone lymphoma (SMZL), nodal marginal zone lymphoma (NMZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and hairy cell leukemia (HCL). In this study, we analyzed the frequency of MYD88 L265P mutation and its correlation with clinico-hematological profile in mature B-cell neoplasms. METHODS: A total of 110 consecutive cases of B-cell neoplasms showing peripheral blood and/or bone marrow infiltration were included. MYD88 L265P mutation was detected by polymerase chain reaction amplification of exon 5 of MYD88 gene, followed by restriction fragment length polymorphism analysis. RESULTS: Among the 110 cases, the major group was of CLL (54.5%, n = 60), followed by HCL. Other cases included MCL, LPL, DLBCL, SMZL, NMZL, FL, and BL. MYD88 L265P mutation was seen in 21 (19.1%) cases of B-cell neoplasm, whereas 89 (80.9%) cases were negative for MYD88 L265P mutation. It was most commonly seen in LPL/WM cases followed by HCL, SMZL, CLL, and MCL cases. No case of DLBCL, FL, and BL showed MYD88 L265P mutation. Statistically significant difference was seen for hemoglobin level in CLL cases, with MYD88 L265P mutated cases showing higher mean hemoglobin levels than MYD88 wild-type cases (p = .001). For other parameters, no statistically significant difference was noted between mutated and unmutated cases. CONCLUSION: MYD88 L265P mutation is seen in various B-cell neoplasms; it is most commonly seen in LPL/WM cases but not specific for it.
The epidemiology of lymphoma in Jordan: A nationwide population study of 4189 cases according to World Health Organization classification system.
Aladily TN, Khreisat W, Ashukhaibi O … +13 more , Alkhatib SM, Annab H, Tarawneh MS, Salman TS, Abu Farsakh H, Mahgoub R, Bustami N, Mansour AT, Aldeen AlRyalat S, Abbadi AS, Al-Fararjeh F, Sughayer M, Jaber O
Hematol Oncol Stem Cell Ther · 2021 Dec · PMID 33212024 · Publisher ↗
OBJECTIVE/BACKGROUND: Lymphoma is a common human cancer that shows a variable geographic incidence worldwide. It is the fourth most common cancer in Jordan. Systemic reports of descriptive epidemiology on lymphoma from t...
OBJECTIVE/BACKGROUND: Lymphoma is a common human cancer that shows a variable geographic incidence worldwide. It is the fourth most common cancer in Jordan. Systemic reports of descriptive epidemiology on lymphoma from the Middle East are limited. METHODS: A nationwide multi-institutional retrospective study was conducted covering all major hospitals and laboratories that provide diagnostic services. We collected data on all cases diagnosed with lymphoma between 2014 and 2019. The included variables were patients' age, gender, anatomic site, and the histologic type according to the World Health Organization classification system. RESULTS: A total of 4189 cases were diagnosed with lymphoma. There was a statistically significant gender difference (p < .05), as 57.5% of patients were males. The peak incidence occurred at age 25-55 years. There were 1,652 (39%) cases of Hodgkin lymphoma (HL) and 2,537 (61%) of non-Hodgkin lymphoma (NHL), where nodular sclerosis (67%) and diffuse large B-cell lymphoma (53%) were the most common subtypes, respectively. The average age-adjusted incidence rates per 100,000 population were 8.01 for all lymphomas, 4.33 for NHL, and 3.16 for HL and all remained stable over the 6 years. CONCLUSION: HL is the most common lymphoma in Jordan, with a percentage higher than most of reported studies in Asian and Western countries. It also shows a unimodal distribution of age-specific incidence rates, with a single peak in young adults. The incidence rate of HL is higher than Eastern countries but comparable to the West. In contrast, NHL demonstrates a lower incidence rate than Western countries but a similar distribution of subtypes, as mature T/natural killer-cell lymphomas were rare.
Hepatitis-Associated Aplastic Anemia.
Alshaibani A, Dufour C, Risitano A … +2 more , de Latour R, Aljurf M
Hematol Oncol Stem Cell Ther · 2022 Jun · PMID 33197413 · Publisher ↗
Hepatitis-associated aplastic anemia (HAAA) is a rare illness, characterized by onset of pancytopenia with a hypoplastic bone marrow that traditionally occurs within 6 months of an increase in serum aminotransferases. HA...
Hepatitis-associated aplastic anemia (HAAA) is a rare illness, characterized by onset of pancytopenia with a hypoplastic bone marrow that traditionally occurs within 6 months of an increase in serum aminotransferases. HAAA is observed in 1% to 5% of all newly diagnosed cases of acquired aplastic anemia. Several hepatitis viruses have been linked to the disease, but in many cases no specific virus is detected. The exact pathophysiology is unknown; however, immune destruction of hematopoietic stem cells is believed to be the underlying mechanism. HAAA is a potentially lethal disease if left untreated. Management includes immunosuppression with antithymocyte globulin and cyclosporine and allogeneic hematopoietic stem cell transplantation.
C-reactive protein and ferritin levels and length of intensive care unit stay in patients with B-cell lymphomas treated with axicabtagene ciloleucel.
Melody M, Rahman ZA, Saunders H … +11 more , Diaz PL, Gannon N, Rosenthal A, Ayala E, Tun HW, Murthy H, Roy V, Foran J, Castro JE, Guru P, Kharfan-Dabaja MA
Hematol Oncol Stem Cell Ther · 2021 Jun · PMID 33069694 · Publisher ↗
OBJECTIVE/BACKGROUND: Chimeric antigen receptor (CAR) T-cell is an effective therapy in relapsed/refractory large B-cell lymphomas that, due to its unique toxicities, often requires escalation of care to the intensive ca...
OBJECTIVE/BACKGROUND: Chimeric antigen receptor (CAR) T-cell is an effective therapy in relapsed/refractory large B-cell lymphomas that, due to its unique toxicities, often requires escalation of care to the intensive care unit (ICU) setting. C-reactive protein (CRP) and ferritin are serum inflammatory markers associated with onset and persistence of CAR T-cell-related toxicity. METHODS: We retrospectively analyzed 34 patients treated with axicabtagene ciloleucel (axi-cel) who were divided into two groups: patients requiring admission to the ICU during initial hospitalization (n = 13, 38%) and those who did not (n = 21, 62%). Primary objective was to examine possible relationships between serum ferritin and/or CRP levels with the need for, and length of, ICU stay between these groups. RESULTS: All 13 patients admitted to the ICU developed cytokine release syndrome (CRS) and 11 of them also developed neurotoxicity (NT). Of the 21 patients in the non-ICU group, 18 developed CRS and 5 patients developed NT. Grade of CRS and NT were higher in ICU versus non-ICU patients (p = .03 and .001, respectively). There was no correlation between CRP levels at time of ICU admission and length of ICU stay (correlation of 0.41, p = .17). Yet, there was an association between serum ferritin levels and length of ICU stay (R = 0.73) which did not reach statistical significance (correlation of 0.21, p = .49). CONCLUSION: Notwithstanding the limitations of the small sample size, our study suggests that an elevated ferritin level at the time of escalation of medical care may be possibly indicative of anticipated prolonged ICU hospitalization in patients treated with axi-cel. A large multicenter study is certainly needed to confirm this observation.
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