Jayakrishnan TT, Bakalov V, Chahine Z
… +3 more, Lister J, Wegner RE, Sadashiv S
Hematol Oncol Stem Cell Ther
· 2021 Sep · PMID 33069693
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BACKGROUND: Disparities driven by socioeconomic factors have been shown to impact outcomes for cancer patients. We sought to explore this relationship among patients with multiple myeloma (MM) who were not considered for...BACKGROUND: Disparities driven by socioeconomic factors have been shown to impact outcomes for cancer patients. We sought to explore this relationship among patients with multiple myeloma (MM) who were not considered for hematopoietic stem cell transplant in the first-line setting and how it varied over time. METHODS: We queried the National Cancer Database for patients diagnosed with MM between 2004 and 2016 and included only those who received systemic therapy as the first-line treatment. Enrollment rates for therapy were calculated as receipt of systemic therapy as the incident event of interest (numerator) over time to initiation of therapy (denominator) and used to calculate incident rate ratios that were further analyzed using Poisson regression analysis. A multivariate Cox proportional hazards model was constructed for survival analysis, and differences were reported as hazard ratios (HRs). RESULTS: We identified 56,102 patients for enrollment analysis and 50,543 patients for survival analysis. Therapy enrollment in a multivariate model was significantly impacted by race and sex (p < .005). Advanced age, earlier year of diagnosis, lack of insurance or Medicaid, and higher comorbidity were associated with poor survival (HR > 1), whereas female sex, non-Hispanic black race, higher income, and treatment at an academic center were associated with improved survival (HR < 1). CONCLUSION: Disparities in treatment of MM exist and are caused by a complex interplay of multiple factors, with socioeconomic factor playing a significant role. Studies exploring such determinants may help in equitable distribution of resources to overcome such differences.
OBJECTIVE/BACKGROUND: Individuals with sickle cell anaemia (SCA) may manifest various forms of renal abnormalities. Proteinuria is an early marker of renal dysfunction and a strong risk factor for chronic kidney disease...OBJECTIVE/BACKGROUND: Individuals with sickle cell anaemia (SCA) may manifest various forms of renal abnormalities. Proteinuria is an early marker of renal dysfunction and a strong risk factor for chronic kidney disease (CKD) progression in both patients with SCA and non-SCA population. Currently, the degree of attention given to proteinuric CKD far exceeds that of nonproteinuric CKD, and risk factors that might trigger a progressive decline of the glomerular filtration rate (GFR) in the absence of proteinuria have not been well evaluated in SCA. The aim of this study was to compare the clinical and laboratory parameters among SCA patients with proteinuric and nonproteinuric CKD. METHODS: This was a cross-sectional study conducted at the University of Maiduguri Teaching Hospital in north-eastern Nigeria between January 2013 and April 2018. Clinical variables including age of diagnosis of SCA, frequency of vaso-occlusive crises, number of hospitalizations per annum and transfusion therapy were collected. Laboratory data including haematological profile and renal function test were obtained from routine blood sampling. RESULTS: A total of 257 patients with SCA (HbSS) were enrolled during the study period of which 42 had proteinuric CKD, and 48 had nonproteinuric CKD. The two groups were matched for the number of hospital admission (p = .063) and blood transfusion per year (p = .450), frequency of painful crisis (p = .210), systolic blood pressure (p = .084) and diastolic blood pressure (p = .400). In the proteinuric CKD group, the mean serum creatinine was higher (332.17 µmol/L, p = .001) and the estimated GFR was lower (31.88 mL/min, p = .046). The serum alkaline phosphatase was higher in the nonproteinuric CKD group (81.81 IU/L, p = .012). CONCLUSION: Nonproteinuric CKD was more frequent than proteinuric CKD in our study population; however, the proteinuric group presented with more advanced disease.
Abid MB, Chhabra S, Buchan B
… +6 more, Graham MB, Abedin S, Thapa B, D'Souza A, George B, Hamadani M
Hematol Oncol Stem Cell Ther
· 2021 Mar · PMID 33058787
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OBJECTIVE/BACKGROUND: A few case reports in the setting of coronavirus disease 2019 (COVID-19) and multiplex polymerase chain reaction (PCR)-based assays for common respiratory pathogens have shown a higher yield of bron...OBJECTIVE/BACKGROUND: A few case reports in the setting of coronavirus disease 2019 (COVID-19) and multiplex polymerase chain reaction (PCR)-based assays for common respiratory pathogens have shown a higher yield of bronchoalveolar lavage (BAL) samples than upper airway specimens in immunocompromised patients. METHODS: A retrospective study was conducted reviewing patients diagnosed with COVID-19 at the Medical College of Wisconsin (Milwaukee, WI, USA) between March 13, 2020 and June 11, 2020. All patients tested positive for SARS-CoV-2 via real-time reverse transcriptase PCR (RT-PCR), through a nasopharyngeal or a bronchoscopy specimen. RESULTS: During the study period, 53 bronchoscopy procedures were performed at the institution, of which five patients tested positive for COVID-19. Of the five patients, three underwent BAL testing based on high clinical suspicion for COVID-19 after the nasopharyngeal (NP) swab(s) was negative. All three patients had underlying cancers and had lymphopenia for a considerable duration prior to being diagnosed with COVID-19. Two patients had better outcomes that could be attributed to earlier BAL specimen testing resulting in timely medical intervention. CONCLUSION: This study underscores the need for early lower respiratory tract sampling, whenever possible, in patients with cancer and prolonged lymphopenia. High clinical suspicion ought to supersede false-negative NP reverse transcriptase-PCR as early bronchoscopic evaluation in cancer patients, who are either receiving active treatment or are immunosuppressed, can allow timely institution of efficacious treatment, enrollment into clinical trials, as well as effective infection control. In the apt clinical setting in patients with cancer, presumptive treatment may also be considered to minimize exposure to healthcare providers and proceduralists.
Vasudevan Nampoothiri R, Chen S, Pasic I
… +10 more, Al-Shaibani Z, Lam W, Michelis FV, Kim DDH, Viswabandya A, Gerbitz A, Lipton JH, Kumar R, Mattsson J, Law AD
OBJECTIVE/BACKGROUND: Unsuccessful cytogenetic (US) analysis at baseline has been reported to be a poor prognostic feature in patients with acute myeloid leukemia (AML). We conducted this study to examine the prognostic...OBJECTIVE/BACKGROUND: Unsuccessful cytogenetic (US) analysis at baseline has been reported to be a poor prognostic feature in patients with acute myeloid leukemia (AML). We conducted this study to examine the prognostic impact of UC/inconclusive cytogenetic analysis on outcomes in patients with AML undergoing allogeneic hematopoietic stem cell transplantation (Allo HSCT). METHODS: We retrospectively analyzed all adults undergoing Allo HSCT for AML from January 2011 to August 2019. Patients with any documented cytogenetic abnormalities were excluded. Baseline characteristics and transplant outcomes were compared between patients with normal cytogenetics and those with UC. RESULTS: Overall, 243 AML patients (median age, 55 years; 55.1% female) were included. UC were reported in 79 patients, whereas 164 patients had a normal karyotype. The two groups were similar to each other in terms of baseline demographics, treatment received, and transplant related variables. There was no difference between patients with UC and normal cytogenetics in terms of relapse-free survival (66 months vs. 42 months, p = .53) or overall survival (OS; 77 months vs. 76 months, p = .72). Survival parameters remained similar even in subgroup analysis based on NPM1 and FLT3 mutation status. Significant predictors of OS after Allo HSCT in AML patients with UC were increased age at time of Allo HSCT (hazard ratio [HR] = -1.049; 95% confidence interval [CI], 1.005-1.095), favorable (NPM1/FLT3) mutation profile (HR = 0.11; 95% CI, 0.01-0.84), neutrophil engraftment < 17 days, and absence of chronic graft-versus-host disease (HR = 3.27; 95% CI, 1.20-8.60). CONCLUSION: Outcomes after Allo HSCT are comparable between AML patients with UC analysis and patients with normal cytogenetics even after stratification based on molecular risk factors. Allogeneic Allo HSCT may mitigate the poor prognosis of UC analysis in patients with AML.
BACKGROUND: Vitamin D is a steroid hormone that exerts its actions through ligation of the vitamin D receptor (VDR), a transcription factor of the nuclear receptor family. VDR has not only physiologic actions in calcium...BACKGROUND: Vitamin D is a steroid hormone that exerts its actions through ligation of the vitamin D receptor (VDR), a transcription factor of the nuclear receptor family. VDR has not only physiologic actions in calcium metabolism but also several other cellular effects through extensive binding to the DNA and modification of genome expression. In cancer, it has neoplasia-suppressive effects and various mechanisms of action mediating cancer cell inhibition have been described. Vitamin D deficiency has been linked to increased risk of breast cancer. A role of the vitamin once the disease has been diagnosed is also probable. METHODS: A systematic review and meta-analysis of studies that report on vitamin D levels (in the form of its main circulating metabolite, 25-hydroxyvitamin D [25-OHD]) in patients with newly diagnosed breast cancer was performed. Outcomes of interest included the levels of serum 25-OHD in patients with breast cancer, those of matched controlled, in studies that included controls, as well as respective percentages of patients and controls with deficient and insufficient 25-OHD levels. RESULTS: A total of 25 studies (10 with controls and 15 without controls) provided data on the outcomes of interest. Populations from all continents, besides Australia, were represented in the studies. The mean level of 25-OHD in patients with breast cancer was 26.88 ng/mL (95% CI 22.8-30.96 ng/mL) and the mean level of 25-OHD in control patients was 31.41 ng/mL (95% CI 19.31-43.5 ng/mL). In the patients with breast cancer group, 45.28% (95% CI 24.37%-53.51%) had levels of 25-OHD below 20 ng/mL, whereas this percentage was 33.71% (95% CI 21.61%-45.82%) in controls. Similarly, 67.44% (95% CI 48.32%-86.55%) of patients with breast cancer had a baseline level of 25-OHD below 30 ng/mL, whereas this percentage was 33.71% (95% CI 21.61%-45.82%) in controls. CONCLUSION: A high prevalence of vitamin D insufficiency is observed in patients with newly diagnosed breast cancer and may be linked pathophysiologically with breast cancer development or progression. Therapeutic benefits may be provided by manipulation of the vitamin D pathway in breast cancer.
OBJECTIVE/BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a treatment for benign and malignant hematological diseases. These aggressive treatments cause reduced levels of physical activity, decreased lung f...OBJECTIVE/BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a treatment for benign and malignant hematological diseases. These aggressive treatments cause reduced levels of physical activity, decreased lung function, and worse quality of life. Alterations in pulmonary function tests before HSCT are associated with the risk of respiratory failure and early mortality. The objective of this study was to evaluate functional capacity and lung function before and after HSCT and identify the predictors of mortality after 2 years. METHODS: A prospective cohort study was carried out with individuals with oncohematological diseases. The evaluations were carried out in two moments during hospitalization and at hospital discharge. Follow-up was carried out after 48 months. Assessments were carried out on 34 adults, using spirometry, manovacuometry, 6-Minute Walk Test (6MWT), Handgrip Strength Test, and 30-Second Chair Stand Test (30-s CST). RESULTS: There was a statistically significant reduction for the variables in forced vital capacity, forced expiratory volume predicted in the 1st second, Tiffeneau index, handgrip strength, and distance covered (% predicted) on the 6MWT (p < .05). There was a significant difference in the 30-s CST when individuals were compared according to the type of transplant. We found that a 10% reduction in the values of maximum inspiratory pressure (MIP) can predict an increased risk for mortality. CONCLUSIONS: Individuals undergoing HSCT have reduced functional capacity, lung function, and muscle strength during the hospitalization phase. Reduction in the values of MIP increases the risk of nonrelapse mortality.
AIM: In chronic myeloid leukemia (CML), the impact of MBCR-ABL1 major transcript type on disease phenotype and response to treatment still controversial to date. This work aims to study the influence of Mb3a2 and Mb2a2 t...AIM: In chronic myeloid leukemia (CML), the impact of MBCR-ABL1 major transcript type on disease phenotype and response to treatment still controversial to date. This work aims to study the influence of Mb3a2 and Mb2a2 transcripts on clinico-biological parameters and the molecular response in patients with chronic phase chronic myeloid leukemia (CP-CML) treated with Imatinib as frontline therapy. METHODS: This is six years prospective study started in March 1 st, 2013. 67 patients with newly CP-CML were treated by Imatinib as frontline therapy. Clinical and biological characteristics disease were collected for all patients. Molecular typing was performed by multiplex RT-PCR and quantification of transcripts by real-time quantitative PCR (qRT-PCR). The cumulative incidence of deep molecular response (DMR) was estimated by the Kaplan-Meier method. The comparison was made using the parametric Log-Rank test. A value of P ≤ 0.05 is considered significant. RESULTS: 61% of patients expressed b3a2, 35.82% b2a2 and 2.98% expressed a rare transcript of type e19a2. At diagnosis, the b2a2 type had a higher level of expression than that of b3a2 (67.92 vs 53.79%; P = 0.03). This insignificant difference between the two transcript subgroups was also observed for rates below 1% at 6 months (54 vs 39; P = 0.26) and below 0.1% (54 vs 44 %; P = 0.50), (77 vs 50%; P = 0.09) and (81 vs 78 %; P = 0.52) at 12, 18 and 24 months respectively. The two types of transcript had almost the same kinetics. Nevertheless, the absolute value of the BCR-ABL1/ABL ratio decrease was faster in the group of patients expressing b3a2, than in those expressing b2a2. At 18 months post IM therapy, patients with a b3a2 transcript have a trend of better MMR that those with b2a2 (77 vs 50%; P = 0.09). The DMR was not significantly different between two groups at 24 months (50 vs 32%; P = 0.20) and 36 months (75 vs 70%; P = 0.54) respectively. The cumulative probability of achieving MRD at 5 years was higher in patients with b3a2 type but not statistically significant; (85 vs. 68%; P = 0.17). CONCLUSION: Patients with b3a2 transcript may be associated with a better response to Imatinib therapy.
Glioblastoma (GB) is one of the most malignant types of central nervous system tumours, classified as grade IV by the World Health Organization. Despite the therapeutic advances, the prognosis is ominous, with a median s...Glioblastoma (GB) is one of the most malignant types of central nervous system tumours, classified as grade IV by the World Health Organization. Despite the therapeutic advances, the prognosis is ominous, with a median survival of about 12-15 months post diagnosis. Although therapeutic options available can increase the survival, they are ineffective in treating patients with GB. Impairing factors such as the blood-brain barrier, cancer stem cells, and infiltration into brain parenchyma lead to failure of current therapies. Therefore, clinicians need novel/alternative effective strategies to treat GB. Due to their ability to preserve healthy tissues and to provide an effective and long-lasting response, stem cells (SCs) with tropism for tumour cells have attracted considerable attention in the scientific community. As is the case here, SCs can be used to target brain tumour cancer cells, especially high-grade malignant gliomas like GB, by overcoming the resistance and exerting benefits for patients affected with such lethal disease. Herein, we will discuss the research knowledge regarding SC-based therapy for the treatment of GB, focalising our attention on SCs and SC-released extracellular vesicles modified to express/load different antitumour payloads, as well as on SCs exploited as a diagnostic tool. Advantages and unresolved issues of anticancer SC-based therapy will also be considered.
Shaheen M, Almohareb F, Aljohani N
… +31 more, Ayas M, Chaudhri N, Abosoudah I, Alotaibi S, Alshahrani M, Alsharif F, Akhtar S, Alhumaidan H, Rasheed W, Alfraih F, Al-Anazi K, Alhashmi H, Al-Daama S, Hanbali A, Alsaleh K, Alzahrani H, Ibrahim K, Alawwami M, Albeirouti B, Albeihany A, Alabdulwahab A, Motabi I, Zaidi SZA, Ahmed SO, Aljefri A, Hussain F, Alahmari A, Hashmi S, Elsolh H, Alseraihy A, Aljurf M
Saudi Arabia is the largest of the Arabian Gulf countries with a total population of 33.41 million as of 2017. This report summarizes the experience from four leading tertiary care hematopoietic stem cell transplantation...Saudi Arabia is the largest of the Arabian Gulf countries with a total population of 33.41 million as of 2017. This report summarizes the experience from four leading tertiary care hematopoietic stem cell transplantation (HSCT) centers in Saudi Arabia representing more than 90% of all HSCTs performed in the country. Between 1984 and 2016, a total of 6,184 HSCTs were performed. Of these, 3,586 HSCTs were performed in adults and 2,598 HSCTs were performed in pediatric patients. Malignancy was the main indication for transplantation (47%). While most transplants were performed from an identical sibling donor, HSCTs from cord blood, unrelated and, more recently, haploidentical donors have also been performed. Relative shortage of HSCT bed capacity is perceived to be a limiting factor in Saudi Arabia. Lately, more HSCT centers are emerging with rapid growth, which may significantly improve the access to HSCT in the country in the near future.
While umbilical cord blood is increasingly utilized as a stem cell source, immune complications associated with the procedure have been recognized. These complications result from significant immune system dysregulation...While umbilical cord blood is increasingly utilized as a stem cell source, immune complications associated with the procedure have been recognized. These complications result from significant immune system dysregulation and defective reconstitution following transplant causing an imbalance between T-cell subsets, aberrant B cells, and abnormal antibody production. This may occur up to 12 months after transplant coinciding with thymic regeneration in adults. The aim of our review is to describe the incidence, pathophysiology, clinical features, and prognosis of autoimmune cytopenias following umbilical cord blood transplant. Furthermore, we review the treatment strategies reported in the existing literature, describe the authors' experience with the complication, and highlight novel treatment options being studied. The knowledge of the occurrence and timing of autoimmune complications of umbilical cord blood transplantation is essential for detection and treatment of the disease. Emerging therapeutic options include interleukin-2 (IL-2), which is also being studied for the treatment of acute and chronic graft-versus-host disease. IL-2 has favorable effects on growth, differentiation, and function of regulatory T cells. Monoclonal antibody treatments, such as daratumumab, are also on the forefront and more experience with them will guide further treatment strategies.
The present study aimed to investigate the cytotoxic effect of 38 new thiosemicarbazone derivatives on hematological neoplastic cells lines and to select the most effective compounds to investigate the main molecular mec...The present study aimed to investigate the cytotoxic effect of 38 new thiosemicarbazone derivatives on hematological neoplastic cells lines and to select the most effective compounds to investigate the main molecular mechanisms involved in cell death. Cytotoxicity screening on Daudi and Jurkat cells revealed that only compound 1b met the selection criteria; therefore, it was chosen for further investigation. Cell viability of Daudi, Jurkat, Molt-4, Namalwa, K562, and MM.1S cell lines decreased in a concentration- and time-dependent manner after compound1b incubation; nevertheless the compound neither caused significant hemolysis nor reduction in peripheral blood mononuclear cell viability. Although no changes were observed on cell cycle or Ki-67 expression, compound1b induced apoptotic-like cell death with mitochondrial involvement, Bax/Bcl-2 inversion, AIF release, survivin inhibition, and caspase-3 activation in both Daudi and Jurkat cells. Furthermore, the compound reduced NFκB expression in Jurkat cells. In Daudi cells, compound1b also decreased CHOP, Akt, pAkt, and MAPK/ERK2 expression, thereby suggesting modulation of UPR, PI3K/Akt/mTOR, and MAPK/ERK signaling pathways. Finally, the compound was able to reduce the cell viability of samples collected from patients with different lymphoid neoplasms subtypes, showing that thiosemicarbazones derivatives could be used in the development of new drugs with anticancer activity.
OBJECTIVE/BACKGROUND: The purpose of this study was to evaluate serum cardiac troponin I and serum N-terminal (NT) pro-brain natriuretic peptide (pro-BNP) levels and the utility of tissue Doppler imaging in assessing car...OBJECTIVE/BACKGROUND: The purpose of this study was to evaluate serum cardiac troponin I and serum N-terminal (NT) pro-brain natriuretic peptide (pro-BNP) levels and the utility of tissue Doppler imaging in assessing cardiovascular changes following left ventricular (LV) dysfunction in children with beta-thalassemia major (β-TM). In children with β-TM who depend on regular blood transfusion, cardiac iron toxicity is a common serious complication. The most common cause of death among these patients is congestive heart failure. METHODS: This is a cross-sectional study which included 50 patients with β-TM and 50 healthy controls. Tissue Doppler imaging was performed and levels of serum ferritin, cardiac troponin I, and NT pro-BNP were estimated for all included patients. RESULTS: Serum NT pro-BNP and cardiac troponin (cTnI) showed a significant increase in patients with β-TM (p < .001). In patients with β-TM, LV dimensions (LV end systolic diameter) and (LV end diastolic diameter) were large (p < .01); LV mass (p < .01), E wave, and E/A ratio (p < .01) were high (p < .05); and deceleration time was short (p < .05). Besides, transmitral ratio (E/E) (p < .05) and tricuspid valve velocity were higher (p < .05), and early diastolic velocity (E) (p < .05) and systolic wave velocity (S) were lower in patients with β-TM (p < .05). A significant positive correlation was detected between the pro-BNP and E wave (r = 0.558, p < .001), E/A ratio (r = 0.403, p < .001), E/E ratio (r = 0.576, p < .001), and ferritin (r = 0.545, p < .001). CONCLUSION: Pulsed wave tissue Doppler imaging and NT pro-BNP had a significant role in the estimation of ventricular dysfunction in children with β-TM.
Samarkandi H, Al Nahedh M, Alfattani A
… +15 more, Alsharif F, Bakshi N, Rasheed W, Alfraih F, Alhumaid M, Alkhudair N, Alhayli S, Alsaedi H, Shaheen M, Hanbali A, Hashmi SK, Devol E, Alseraihy A, Alzahrani H, Aljurf M
BACKGROUND: Thrombocytopenia remains a life-threatening late complication of HCT with an incidence of 5-20%. Currently, there is no approved drug for the treatment of persistent thrombocytopenia post HCT and platelet tra...BACKGROUND: Thrombocytopenia remains a life-threatening late complication of HCT with an incidence of 5-20%. Currently, there is no approved drug for the treatment of persistent thrombocytopenia post HCT and platelet transfusion is the maintain stay of treatment. Eltrombopag is approved for the treatment of thrombocytopenia associated with different diseases, however; data on eltrombopag treatment post HCT are limited. METHODS: This is a retrospective cohort study evaluating the effect of eltrombopag on platelet recovery in patients with persistent thrombocytopenia post HCT. The primary endpoint was platelet recovery to ≥ 20,000/μL for 7 consecutive days without transfusion support after starting eltrombopag. Secondary endpoint was platelet recovery to ≥ 50,000/μL for 7 consecutive days. RESULTS: Twenty-one patients were included. Twelve (75%) of 16 patients became independent from platelet transfusions. Median time from starting eltrombopag to last transfusion was 60 days (range, 9-226 days). Ten (63%) of 16 transfusion dependent patients with platelet count < 20,000/μL achieved the primary endpoint. Seven (33%) patients of 21 included had successful platelet recovery (ie, ≥50,000/μL without transfusion support) and the median time to platelet recovery in patients who achieved it was 32 days (range, 13-265 days). Ten patients (48%) were able to successfully discontinue eltrombopag without recurrence of thrombocytopenia. CONCLUSION: Our findings demonstrated that eltrombopag appears to have a clinically significant impact on platelet recovery in persistent thrombocytopenic patients post HCT.
OBJECTIVE/BACKGROUND: Acute myeloid leukemia (AML) is one of the common forms of hematological malignancy and acute promyelocytic leukemia (APL) is a unique subtype of AML conferring favorable prognosis. We aimed to dete...OBJECTIVE/BACKGROUND: Acute myeloid leukemia (AML) is one of the common forms of hematological malignancy and acute promyelocytic leukemia (APL) is a unique subtype of AML conferring favorable prognosis. We aimed to determine the prevalence and prognostic impact of Fms-like tyrosine kinase 3 (FLT3), nucleophosmin 1 (NPM1) mutation, epidermal growth factor receptor (EGFR), and flow marker's expression in patients with APL. METHODS: In the present study, 165 de novo APL patients were molecularly characterized for promyelocytic leukemia (PML) breakpoint and additional genetic alterations. Reverse transcriptase polymerase chain reaction (PCR) and real-time PCR assays were used to detect genetic alterations. RESULTS: PML/RARα was detected in 29/165 (17.5%) samples with breakpoint cluster region 1 (bcr1) in 17/29 (58.5%) and bcr3 in 12/29 (41.5%) samples. The prevalence of FLT3-ITD, NPM1, and EGFR were detected in 5/29 (17.5%), 11/29 (38%), and 5/29 (17.5%) patients, respectively. Patients expressing bcr-3 hybrid transcript had lower overall survival compared with bcr1 ( p = .254). White blood cell (WBC) count was significantly higher in bcr3 in comparison with bcr1 patients ( p = .002). Patients with positive EGFR expression ( p = .042) and higher WBC ( p = .002) were significantly associated with poor survival ( p < .05). CONCLUSIONS: We documented the higher prevalence of bcr1 and confirmed that the association of FLT3-ITD significantly reduced the chances of survival in APL. The mortality rate of bcr3 was comparatively higher than that of bcr1. Higher WBC count and EGFR expression were significantly associated with poor survival.
ElGohary GM, Hashmi S, Styczynski J
… +14 more, Kharfan-Dabaja MA, Alblooshi RM, de la Cámara R, Mohmed S, Alshaibani A, Cesaro S, Abd El-Aziz N, Almaghrabi R, Gergis U, Majhail NS, El-Gohary Y, Chemaly RF, Aljurf M, El Fakih R
Hematol Oncol Stem Cell Ther
· 2022 Jun · PMID 32745466
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Numerous studies have been published regarding outcomes of cancer patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causing the coronavirus disease 2019 (COVID-19) infection. H...Numerous studies have been published regarding outcomes of cancer patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causing the coronavirus disease 2019 (COVID-19) infection. However, most of these are single-center studies with a limited number of patients. To better assess the outcomes of this new infection in this subgroup of susceptible patients, we performed a systematic review and meta-analysis to evaluate the impact of COVID-19 infection on cancer patients. We performed a literature search using PubMed, Web of Science, and Scopus for studies that reported the risk of infection and complications of COVID-19 in cancer patients and retrieved 22 studies (1018 cancer patients). The analysis showed that the frequency of cancer among patients with confirmed COVID-19 was 2.1% (95% confidence interval [CI]: 1.3-3) in the overall cohort. These patients had a mortality of 21.1% (95% CI: 14.7-27.6), severe/critical disease rate of 45.4% (95% CI: 37.4-53.3), intensive care unit (ICU) admission rate of 14.5% (95% CI: 8.5-20.4), and mechanical ventilation rate of 11.7% (95% CI: 5.5-18). The double-arm analysis showed that cancer patients had a higher risk of mortality (odds ratio [OR]=3.23, 95% CI: 1.71-6.13), severe/critical disease (OR=3.91, 95% CI: 2.70-5.67), ICU admission (OR=3.10, 95% CI: 1.85-5.17), and mechanical ventilation (OR=4.86, 95% CI: 1.27-18.65) than non-cancer patients. Furthermore, cancer patients had significantly lower platelet levels and higher D-dimer levels, C-reactive protein levels, and prothrombin time. In conclusion, these results indicate that cancer patients are at a higher risk of COVID-19 infection-related complications. Therefore, cancer patients need diligent preventive care measures and aggressive surveillance for earlier detection of COVID-19 infection.
Carfilzomib is an irreversible proteasome inhibitor currently approved for the treatment of relapsed multiple myeloma. It has been implicated as a cause of thrombotic microangiopathy (TMA) in several case reports. The in...Carfilzomib is an irreversible proteasome inhibitor currently approved for the treatment of relapsed multiple myeloma. It has been implicated as a cause of thrombotic microangiopathy (TMA) in several case reports. The incidence, risk factors, and treatment of carfilzomib-related TMA remain unclear. Here we describe the clinical presentation and outcome of a 58-year-old man with biopsy-proven TMA that occurred following treatment with carfilzomib-based therapy. We also reviewed the published literature with regard to the incidence, risk factors, treatment options, and outcome of carfilzomib-related TMA.
BACKGROUND: Acute promyelocytic leukemia is a peculiar disease with few studies that have investigated the prognostic significance of PML/RARA transcript level at diagnosis. PATIENTS AND METHODS: This retrospective study...BACKGROUND: Acute promyelocytic leukemia is a peculiar disease with few studies that have investigated the prognostic significance of PML/RARA transcript level at diagnosis. PATIENTS AND METHODS: This retrospective study included all cases diagnosed with acute promyelocytic leukemia over the period from June 2015 to March 2019. The normalized copy number (NCN) was tested by real-time polymerase chain reaction at diagnosis, and at the end of induction regimen. RESULTS: Our study included 83 de novo APL patients, 53 (63.9%) were adults and 30 (36.1%) were children. The median (range) age of our patients was 28.0 (1.0-70.0) years. The pediatric group had a significantly higher prevalence in males (p = 0.02), higher incidence of disseminated intravascular coagulopathy (p = 0.014), and high-risk groups (p = 0.017). At diagnosis, the median NCN (%) of the entire group at 22.5 was set as the cut off value. There was no significant association between NCN at diagnosis and other prognostic variables except for bone marrow promyelocytes (p = 0.006). High-risk group APL patients as well as those presenting with hemorrhage had an inferior overall survival (OS) (p = 0.007; p < 0.001) respectively. PML-RARA NCN at diagnosis did not have an impact on the OS or increased risk of relapse of our patients (p = 0.434; p = 0.721). CONCLUSION: the initial PML/RARA tumor burden is not a prognostic factor for APL. The initial TLC at 10x10/L cut off is the most important predictive for OS. Early detection and close monitoring are required to decrease the high rate of early deaths in developing countries.
The frontline treatment for patients younger than 40 years with severe aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-identical sibling donor. However, in...The frontline treatment for patients younger than 40 years with severe aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-identical sibling donor. However, in patients with severe AA who are older than 40 years, allogeneic HSCT has been found to be associated with increased treatment-related mortality and toxicity, even when matched sibling donors are used. We report our institutional experience with allogeneic HSCT in patients with severe AA between 40 and 50 years. A total of 19 patients with severe AA were included in the study. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. The mean age of patients at the time of transplant was 43.79 years, and 57.9% were male. The mortality rate was 36.8%, attributed to infection (10.5%), relapse (15.8%), and renal failure (5.3%) in all cases. Acute graft-versus-host disease (GVHD) occurred in five patients (26.3%), and chronic GVHD occurred in two patients (10.5%). The 5-year OS was 62% and the 5-year DFS was 52%. We found that the patient's age, platelet level prior to transplantation, and the number of CD3 cells infused for each transplant were independent prognostic factors for OS, and the age and sex of the patient, graft rejection, and platelet level prior to transplantation were significant prognostic factors associated with DFS. We recommend that immunosuppressive therapy be considered as a first-line treatment in patients with severe AA who are older than 40 years. Allogeneic HSCT can be considered a valid alternative option in patients whose suppression therapy fails.
Primary central nervous system lymphoma (PCNSL) is a rare lymphoma that involves the central nervous system. The standard treatment involves chemotherapy with high-dose methotrexate. To the best of our knowledge, this is...Primary central nervous system lymphoma (PCNSL) is a rare lymphoma that involves the central nervous system. The standard treatment involves chemotherapy with high-dose methotrexate. To the best of our knowledge, this is the first reported case of employing checkpoint inhibitor, nivolumab, alone to treat a patient with PCNSL who could not tolerate the induction therapy. In aggressive cases of PCNSL where chemotherapy may become futile, stand-alone checkpoint inhibitors should be considered as the front-line treatment protocol.
Hematol Oncol Stem Cell Ther
· 2022 Dec · PMID 32645300
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BACKGROUND: Lymphopenia, thrombocytopenia, and elevated D-dimer and ferritin levels are frequently reported in patients with severe coronavirus disease 2019 (COVID-19). Here we report a case of cold agglutinin disease (C...BACKGROUND: Lymphopenia, thrombocytopenia, and elevated D-dimer and ferritin levels are frequently reported in patients with severe coronavirus disease 2019 (COVID-19). Here we report a case of cold agglutinin disease (CAD), autoimmune hemolytic anemia (AIHA), and pulmonary embolism as a presentation of COVID-19 infection. CASE REPORT: A 51-year-old African-American woman presented to the emergency room with fever and shortness of breath. She was tachycardic, febrile, and had an oxygen saturation of 88% on room air. Laboratory studies showed hemoglobin (Hb) 5.1 g/dL, D-dimer 4.55 μg/mL, and C-reactive protein 12.3 mg/dL. Computed tomography scan of the chest showed acute pulmonary embolism involving the bilateral lower lobe segmental branches. Her influenza test was negative, but her SARS-CoV-2 test returned positive. Due to severe anemia, she was not started on any anticoagulation. Haptoglobin was low. Direct antiglobulin test returned positive for anticomplement and negative for anti-immunoglobulin G. Cold agglutinin titer was 80. Mycoplasma, Epstein-Barr virus, parvovirus, human immunodeficiency viruses, and acute hepatitis screen were negative. Abdominal and pelvic computed tomography showed a normal liver and spleen without lymphadenopathy. Peripheral blood smear showed red blood cell agglutination. On Day 2, she became hypoxic requiring 6 L oxygen. Since her Hb remained stable, she was started on low-intensity unfractionated heparin. Inflammatory markers subsequently improved and she was weaned off oxygen. Her Hb remained stable at 9 g/dL and she was discharged home. After 2 weeks, her Hb increased to 11 g/dL. CONCLUSION: As exemplified in this case report, COVID-19 infection can lead to thromboembolism, CAD, and AIHA and it should be recognized as a potential etiology to such rare diseases.