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Blood Advances Apr 2022The objectives of this study were to assess the immunogenicity and safety of COVID-19 vaccines in patients with hematologic malignancies. A systematic review and... (Meta-Analysis)
Meta-Analysis
The objectives of this study were to assess the immunogenicity and safety of COVID-19 vaccines in patients with hematologic malignancies. A systematic review and meta-analysis of clinical studies of immune responses to COVID-19 vaccination stratified by underlying malignancy and published from January 1, 2021, to August 31, 2021, was conducted using MEDLINE, EMBASE, and Cochrane CENTRAL. Primary outcome was the rate of seropositivity after 2 doses of COVID-19 vaccine with rates of seropositivity after 1 dose, rates of positive neutralizing antibodies, cellular responses, and adverse events as secondary outcomes. Rates were pooled from single-arm studies while rates of seropositivity were compared against the rate in healthy controls for comparator studies using a random effects model and expressed as a pooled odds ratios with 95% confidence intervals. Forty-four studies (16 mixed group, 28 disease specific) with 7064 patients were included in the analysis (2331 after first dose, 4733 after second dose). Overall seropositivity rates were 62% to 66% after 2 doses of COVID-19 vaccine and 37% to 51% after 1 dose. The lowest seropositivity rate was 51% in patients with chronic lymphocytic leukemia and was highest in patients with acute leukemia (93%). After 2 doses, neutralizing antibody response rates were 57% to 60%, and cellular response rates were 40% to 75%. Active treatment, ongoing or recent treatment with targeted and CD-20 monoclonal antibody therapies within 12 months were associated with poor immune responses to COVID-19 vaccine. New approaches to prevention are urgently required to reduce COVID-19 infection morbidity and mortality in high-risk patient groups that respond poorly to COVID-19 vaccination.
Topics: Antibodies, Neutralizing; COVID-19; COVID-19 Vaccines; Hematologic Neoplasms; Humans; SARS-CoV-2
PubMed: 34852173
DOI: 10.1182/bloodadvances.2021006333 -
The Oncologist Aug 2022This review summarizes the case studies of PCM1-JAK2 fusion tyrosine kinase gene-related neoplasia. Recommended treatment includes JAK2 inhibitors and hematologic stem...
BACKGROUND
This review summarizes the case studies of PCM1-JAK2 fusion tyrosine kinase gene-related neoplasia. Recommended treatment includes JAK2 inhibitors and hematologic stem cell transplantation (HSCT), although the small number of patients has limited study of their efficacy. Herein, we present all available cases in the current searchable literature with their demographics, diagnoses, treatments, and outcomes.
METHODS
PubMed, ScienceDirect, Publons, the Cochrane Library, and Google were searched with the following terms: PCM1-JAK2, ruxolitinib and myeloid/lymphoid.
RESULTS
Sixty-six patients (mean age = 50, 77% male) had an initial diagnosis of myeloproliferative neoplasm (MPN) in 40, acute leukemia in 21 and T-cell cutaneous lymphoma in 5. Thirty-five patients (53%) had completed 5-year follow-up. The 5-year survival for the MPN, acute myelogenous leukemia (AML), acute lymphocytic leukemia, and lymphoma groups are 62.7, 14.9%, 40.0%, and 100%, respectively. Too few patients have been treated with ruxolitinib to draw conclusions regarding its effect on survival while the 5-year survival for MPN patients with or without HSCT was 80.2% (40.3%-94.8%) versus 51.5% (22.3%-74.6%), respectively. The T-cell cutaneous lymphoma patients have all survived at least 7 years.
CONCLUSION
This rare condition may be increasingly detected with wider use of genomics. Ruxolitinib can yield hematologic and molecular remissions. However, HSCT is, at this time, the only potentially curative treatment. Useful prognostic markers are needed to determine appropriate timing for HSCT in patients with MPN. Patients presenting with acute leukemia have a poor prognosis.
Topics: Female; Humans; Janus Kinase 2; Leukemia; Lymphoma; Male; Middle Aged; Myeloproliferative Disorders; Oncogene Proteins, Fusion
PubMed: 35472244
DOI: 10.1093/oncolo/oyac072 -
Therapeutic Advances in Hematology 2024Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological cancer. Due to its low incidence, researchers struggle to gather sufficient... (Review)
Review
BACKGROUND
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological cancer. Due to its low incidence, researchers struggle to gather sufficient prospective data to inform clinical treatment.
OBJECTIVES
We sought to summarize the clinical characteristics and current treatment methods of BPDCN and provide more specific guidance on treatment options.
DESIGN
A systematic literature review using data from 74 Chinese BPDCN patients.
DATE RESOURCES AND METHODS
We retrospectively analyzed the clinical manifestations, treatment response, survival outcomes, and prognostic factors of six BPDCN patients treated at the First Affiliated Hospital of Zhengzhou University and 68 patients described in 28 articles published in the China Knowledge Network database since 2019.
RESULTS
In Chinese patients, the disease occurred with a male-to-female ratio of 2.52 and a median age of onset of 50 years in adults and 10 years in pediatric patients. Immunohistochemical analysis revealed distinctive immune phenotypes of BPDCN cells, characterized by high expression levels of CD4, CD56, CD123, and HLA-DR, while showing minimal to no expression of myeloperoxidase (MPO), CD20, and CD79a. There was no significant difference in the initial complete remission (CR) rate, relapse rate, and the overall survival (OS) time of patients receiving acute myeloid leukemia-like, acute lymphocytic leukemia-like, or non-Hodgkin's lymphoma-like chemotherapy regimens. Univariate analysis identified CD3 expression, male gender, and central nervous system infiltration as hazardous factors. In multivariate analysis, age proved to be an independent prognostic indicator, indicating better prognosis and longer OS time in younger patients. Notably, hematopoietic stem cell transplantation (HSCT) emerged as a significant factor in improving the survival outcomes for individuals diagnosed with BPDCN. However, further investigation is needed to explore the role of HSCT and the best timing for its implementation in pediatric BPDCN patients.
CONCLUSION
Administering HSCT during the initial CR state following inductive chemotherapy might extend the OS and improve the prognosis of patients with BPDCN.
PubMed: 38832237
DOI: 10.1177/20406207241251602 -
The Cochrane Database of Systematic... Oct 2011Consolidation chemotherapy, autologous hematopoietic cell transplantation (HCT) and allogeneic HCT represent potential treatment alternatives for post-remission therapy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Consolidation chemotherapy, autologous hematopoietic cell transplantation (HCT) and allogeneic HCT represent potential treatment alternatives for post-remission therapy in adult acute lymphoblastic leukemia (ALL), but there is genuine uncertainty regarding the optimal approach.
OBJECTIVES
To assess the effect of matched sibling donor vs. no donor status for adults with ALL in first complete remission (CR1).
SEARCH STRATEGY
We performed a search of CENTRAL, MEDLINE and EMBASE electronic databases in September 2010 along with handsearching of literature cited in relevant primary articles, search of abstracts from American Society of Hematology and American Society of Clinical Oncology meetings, as well as consultation with content experts in the field.
SELECTION CRITERIA
Review was performed by two authors, and Inclusion criteria included the following: controlled trials with donor vs. no donor comparison with assignment by genetic randomizationin adults with ALL in CR1.
DATA COLLECTION AND ANALYSIS
We extracted data on benefits (overall survival, progression-free survival) and harms (treatment-related mortality, relapse) of compared treatments. Adverse events were considered, but analysis of individual adverse events was not possible from the reported literature. We pooled summary results from each study using a random-effects model. We assessed heterogeneity. We performed subgroup analyses for disease risk categories. We performed sensitivity analyses according to methodological quality.
MAIN RESULTS
A total of 14 relevant trials were identified, consisting of a total of 3157 patients. There was a statistically significant overall survival advantage in favor of the donor versus no donor group (HR 0.86; 95% CI 0.77 to 0.97; P = 0.01), as well as significant improvement in disease-free survival in the donor group(HR 0.82; 95% CI 0.72 to 0.94; P = 0.004). Those in the donor group had significant reduction in primary disease relapse(RR 0.53; 95% CI 0.37 to 0.76; P = 0.0004) and significant increase in non-relapse mortality(RR 2.8; 95% CI 1.66 to 4.73; P = 0.001). Significant heterogeneity was detected in analysis of relapse (Chi(2) 40.51, df = 6, P < 0.00001; I(2) = 85%). In regard to methodologic quality, the majority of included studies were free of selective reporting, and performed analyses according to intention to treat. Conversely, few reported sample size calculation that informed the study design. While blinding was considered as an important domain of methodological quality, none of the studies reported on whether any of the study personnel were blinded (e.g. subjects, personnel, outcome assessors, data analysts etc). Therefore, we did not consider blinding further in the analysis of methodological quality in this review.
AUTHORS' CONCLUSIONS
The results of this systematic review and meta-analysis support matched sibling donor allogeneic hematopoietic cell transplantation as the optimal post-remission therapy in ALL patients aged 15 years or over. This therapy offers superior overall survival and disease-free survival, and significantly reduces the risk of disease relapse, but does impose an increased risk of non-relapse mortality. Importantly these data are based on adult ALL treated with largely total body irradiation-based myeloablative conditioning and sibling donor transplantation and, therefore, cannot be generalized to pediatric ALL, alternative donors including HLA (human leukocyte antigen) mismatched or unrelated donors, or reduced toxicity or non-myeloablative conditioning regimens.
Topics: Adult; Hematopoietic Stem Cell Transplantation; Histocompatibility; Humans; Living Donors; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Siblings; Transplantation Conditioning; Transplantation, Homologous
PubMed: 21975786
DOI: 10.1002/14651858.CD008818.pub2 -
Blood Advances Mar 2022Chimeric antigen receptor T-cell (CAR-T) therapy has transformed treatment paradigms for relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) in...
Chimeric antigen receptor T-cell (CAR-T) therapy has transformed treatment paradigms for relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) in children and younger adults. We performed a systematic review to investigate the published literature on efficacy and toxicity of CAR-T therapy in adults with r/r B-ALL. We searched MEDLINE, Embase, and the Cochrane Library for prospective interventional studies and included published studies of ≥5 patients with median age at enrollment of ≥18 years. Risk of bias was assessed with a modified Institute of Health Economics tool. A total of 2566 records were assessed; 16 studies involving 489 patients were included in the final analysis. The mean complete remission (CR) rate was 81% and the measurable residual disease (MRD)-negative remission rate was 81% at 4 weeks after CAR-T infusion. With median follow-up across studies of 24 months, the cumulative 12-month probabilities of progression-free survival (PFS) and overall survival (OS) were 37% (95% CI, 26-48) and 57% (95% CI, 49-65), respectively. Relapse occurred in 40.3% of cases; target antigen was retained in 73.2% of relapses. Across studies, any grade of cytokine release syndrome (CRS) occurred in 82% of patients (95% CI, 61-95) and grade 3 or higher CRS in 27% (95% CI, 18-36). Neurotoxicity of any grade occurred in 34% of patients (95% CI, 24-47) and grade 3 or higher in 14% (95% CI, 1-25). In summary, CAR-T therapy achieves high early remission rates in adults with r/r B-ALL and represents a significant improvement over traditional salvage chemotherapy. Relapses are common and durable response remains a challenge.
Topics: Acute Disease; Adult; Antigens, CD19; Burkitt Lymphoma; Cell- and Tissue-Based Therapy; Child; Cytokine Release Syndrome; Humans; Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Receptors, Chimeric Antigen; Recurrence
PubMed: 34610109
DOI: 10.1182/bloodadvances.2020003482 -
British Journal of Haematology May 2009Anthracyclines are used to treat childhood acute lymphoblastic leukaemia (ALL) but non-randomized studies suggest that cardiotoxicity may be a problem. Individual... (Meta-Analysis)
Meta-Analysis Review
Anthracyclines are used to treat childhood acute lymphoblastic leukaemia (ALL) but non-randomized studies suggest that cardiotoxicity may be a problem. Individual patient data from trials in childhood ALL that randomized anthracyclines or methods of reducing cardiotoxicity were analysed by standard meta-analysis methods. Results were grouped and combined according to: addition of an anthracycline to standard therapy, type of anthracycline, mode of administration, and the use of a cardioprotectant. Data from 958 patients in 4 trials, recruiting between 1972 and 1984, showed that addition of an anthracycline reduced bone marrow relapse and, non-significantly, non-bone marrow relapse, resulting in an increased relapse-free interval. However there was a non-significant increase in induction failures, and in deaths in first remission. Event-free survival at 5 years was 56.7% with anthracycline versus 52.8% without (Odds Ratio = 0.91; 95% Confidence Interval = 0.76-1.10; P = 0.3). There were no significant differences found in other treatment comparisons. The limited data from trials did not demonstrate differences in clinically evident cardiotoxicity. Anthracyclines are effective against bone marrow relapse but have not been shown to significantly increase event free survival in childhood ALL. The evidence on type of anthracycline, method of administration or use of cardioprotectant was insufficient to be able to rule out important differences.
Topics: Adolescent; Adult; Anthracyclines; Antibiotics, Antineoplastic; Cardiotonic Agents; Child; Child, Preschool; Disease-Free Survival; Female; Heart Diseases; Humans; Infant; Male; Odds Ratio; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Randomized Controlled Trials as Topic; Remission Induction; Young Adult
PubMed: 19236609
DOI: 10.1111/j.1365-2141.2009.07624.x -
Medicine Jul 2022The SET-CAN/NUP214 fusion gene resulting from chromosomal del(9)(q34.11q34.13) or t(9;9) (q34;q34) has been found in T-cell acute lymphoblastic leukemia (T-ALL), B-cell...
BACKGROUND
The SET-CAN/NUP214 fusion gene resulting from chromosomal del(9)(q34.11q34.13) or t(9;9) (q34;q34) has been found in T-cell acute lymphoblastic leukemia (T-ALL), B-cell acute lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML) and myeloid sarcoma (MS). Furthermore, the SET-CAN/NUP214 fusion gene has been found in the T-ALL cell line LOUCY and the AML line MEGAL. The common features of these cases are insensitivity to chemotherapy and poor prognosis. We reviewed the characteristics and prognostic significance of the SET-CAN/NUP214 fusion gene in hematological malignancies.
METHODS
This systematic literature search was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. With the inclusion and exclusion criteria, we summarized all of the papers and performed a statistical analyses.
RESULTS
In general, the SET-CAN/NUP214 fusion gene is very rare in adult acute leukemia, more frequently found in T-ALL than in other types of leukemia, and more often in males. Flow cytometry data indicated that the markers CD34, CD33, CD13, and CD7 were common in SET-CAN/NUP214 positive acute leukemia, including ALL. Fluorescence in situ hybridization and arrays are important methods for detecting the fusion gene in newly diagnosed patients and can detect chromosomal del(9)(q34) will be detected. The chromosomal karyotype may be normal or complex, and, in terms of survival analysis, transplantation results in a better prognosis than chemotherapy alone.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
The presence of SET-CAN/NUP214 fusion gene may be a Minimal Residual Disease of early recurrence, and it might be a poor indicator of outcome.
LIMITATIONS
The mechanism, clinical characteristics, therapy and prognosis of the SET-CAN/NUP214 fusion gene in hematological malignancies require further research.
Topics: Adult; DNA-Binding Proteins; Hematologic Neoplasms; Histone Chaperones; Humans; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute; Male; Nuclear Pore Complex Proteins; Oncogene Proteins, Fusion; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Transcription Factors
PubMed: 35905214
DOI: 10.1097/MD.0000000000029294 -
Annals of Clinical Microbiology and... Jun 2021Aspergillosis of Central Nervous System (CNS) is a highly lethal infection in patients with leukemia and Stem Cell Transplantation (SCT). (Review)
Review
BACKGROUND
Aspergillosis of Central Nervous System (CNS) is a highly lethal infection in patients with leukemia and Stem Cell Transplantation (SCT).
METHODS
Case reports of CNS aspergillosis in patients with leukemia and SCT published between 1990 and August 2020 were gathered using a structured search through PubMed/Medline.
RESULTS
Sixty-seven cases were identified over the searches of the PubMed bibliographic database and then, 59 cases were included in the final analysis. Europe had the largest share of cases at 57.6% (34 reports), followed by Americas and Asia. Affected patients were predominantly males (58.6%) and the mean age of the patients was 36.1 years, while 62.7% of the patients were under the age of 50 years. The most common leukemia types include Acute Lymphoblastic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), and Acute Myeloid Leukemia (AML) at 43.4%, 27.4%, and 23.5%, respectively. Furthermore, stem cell transplantation was reported in 11 cases. The overall mortality was 33%; however, the attributable mortality rate of CNS aspergillosis was 24.5%. Altered mental status, hemiparesis, cranial nerve palsies, and seizures were the clearest manifestations of infection and lung involvement reported in 57% of the patients. Histopathologic examination led to the diagnosis of infection in 57% of the patients followed by culture (23.7%), galactomannan assay (8.5%), and molecular method (3.3%). Amphotericin B and voriconazole were the most frequently used drugs for infection treatment. Good results were not obtained in one-third of the patients treated by voriconazole. Finally, neurosurgical intervention was used for 23 patients (39%).
CONCLUSION
CNS aspergillosis is a rapidly progressive infection in leukemic patients. Thus, these patients should be followed up more carefully. Furthermore, management of induction chemotherapy, use of different diagnostic methods, and use of appropriate antifungal can lead to infection control.
Topics: Antifungal Agents; Asia; Aspergillosis; Central Nervous System; Databases, Factual; Europe; Female; Humans; Leukemia; Male; Stem Cell Transplantation; Voriconazole
PubMed: 34130699
DOI: 10.1186/s12941-021-00452-9 -
Blood Cancer Journal Jun 2020B-cell maturation antigen (BCMA) plays a critical role in regulating B-cell proliferation and survival. There is evidence for BCMA expression in various hematologic... (Meta-Analysis)
Meta-Analysis
B-cell maturation antigen (BCMA) plays a critical role in regulating B-cell proliferation and survival. There is evidence for BCMA expression in various hematologic malignancies, suggesting that BCMA may play an important role as a biomarker or therapeutic target in these diseases. Given advances in understanding the role of BCMA in B-cell development and the promise of BCMA as a therapeutic target, a systematic review is needed to rigorously assess the evidence for BCMA expression and identify areas of consensus and future research. The objective of this review was to summarize the evidence on BCMA protein and mRNA expression across hematologic malignancies. Using a PubMed database search up to 28 August 2019, a systematic literature review of publications reporting BCMA expression in patients with hematologic malignancies was conducted. Data from published congress abstracts presented at the American Society of Clinical Oncology and the American Society of Hematology were also searched. Studies that assessed BCMA expression (protein or mRNA) in patients of any age with hematologic malignancies were included. A total of 21 studies met inclusion criteria and were included in the review. BCMA was expressed in several hematologic malignancies, including multiple myeloma (MM), chronic lymphocytic leukemia, acute B-lymphoblastic leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma. BCMA was expressed at uniformly high levels across all 13 MM studies and at low to moderate levels in acute myeloid leukemia and acute lymphoblastic leukemia. These results suggest that BCMA is a relevant target in MM as well as in a subset of B-cell leukemia. BCMA expression in Hodgkin lymphoma and NHL varied across studies, and further research is needed to determine the utility of BCMA as an antibody target and biomarker in these diseases. Differences in sample type, timing of sample collection, and laboratory technique used may have affected the reporting of BCMA levels.
Topics: B-Cell Maturation Antigen; Gene Expression Regulation, Neoplastic; Hematologic Neoplasms; Hodgkin Disease; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Multiple Myeloma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; RNA, Messenger
PubMed: 32606424
DOI: 10.1038/s41408-020-0337-y -
Research Square Mar 2021ImportanceThe Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. BTK inhibition was shown to protect against...
ImportanceThe Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. BTK inhibition was shown to protect against lethal influenza-induced acute lung injury in mice. Inhibiting BTK has been hypothesized to ameliorate lung injury in patients with severe coronavirus disease 2019 (COVID-19). ObjectiveTo evaluate the use of BTK inhibitors (BTKinibs) during COVID-19 and assess how they may affect patient outcomes.Evidence ReviewWe searched PubMed, Embase, and Web of Science: Core on December 30, 2020. Clinical studies with at least 5 COVID-19 patients treated with BTKinibs were included. Case reports and reviews were excluded.FindingsOne hundred twenty-five articles were identified, 6 of which met inclusion criteria. Sample size ranged from 6 to 126 patients. Patient populations included subjects hospitalized with COVID-19 (6/6) and admitted to the intensive care unit (5/6). Patient age ranged between 35 and 98 years. Four studies included patients already receiving BTKinibs for their lymphoproliferative disease, 1 for Waldenstrom's macroglobulinemia and 3 for chronic lymphocytic leukemia (CLL). The most common clinical outcomes measured were oxygen requirements (4/6) and hospitalization rate or duration (3/6). Differences in standard-of-care reflected the date of study and pre-existing conditions in the various patient cohorts. Full-dose acalabrutinib was evaluated in 2 studies, one study evaluated full-dose ibrutinib, and another study evaluated both ibrutinib and acalabrutinib. The remainder 2 studies described outcomes in CLL patients on multiple BTKinibs and other CLL-targeted treatments. Three studies showed decreased oxygen requirements in patients who started or continued BTKinibs. All three studies that evaluated hospitalization rate or duration found favorable outcomes in those on BTKinibs. Conclusions and RelevanceBTKinib use was associated with decreased oxygen requirements and decreased hospitalization rates and duration. However, randomized clinical trials are needed to validate the beneficial effects of BTKinibs for acute SARS-CoV-2 infection.
PubMed: 33791689
DOI: 10.21203/rs.3.rs-319342/v1