-
Future Oncology (London, England) Mar 2023Blastic plasmacytoid dendritic cell neoplasm is a rarely occurring hematologic malignancy with a dismal prognosis. We conducted a meta-analysis for a total of 1312... (Meta-Analysis)
Meta-Analysis Review
Blastic plasmacytoid dendritic cell neoplasm is a rarely occurring hematologic malignancy with a dismal prognosis. We conducted a meta-analysis for a total of 1312 patients from 24 retrospective studies. The complete remission (CR) rate of acute lymphoblastic leukemia-like induction chemotherapy was 82%, and the overall survival (OS) was 15.75 months; the CR rate of acute myeloid leukemia-like chemotherapy was 51%, and the OS was 7.18 months; and the CR rate of cyclophosphamide, doxorubicin, vincristine and prednisone-like chemotherapy was 50%, and the OS was 12.06 months. Acute lymphoblastic leukemia-like induction chemotherapy has the best CR rate and OS.
Topics: Humans; Induction Chemotherapy; Retrospective Studies; Hematologic Neoplasms; Acute Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myeloproliferative Disorders; Dendritic Cells
PubMed: 36919853
DOI: 10.2217/fon-2022-0521 -
Blood Jun 2023The benefit associated with the incorporation of vincristine-corticosteroid pulses in maintenance therapy for pediatric acute lymphoblastic leukemia (ALL) is unclear,... (Meta-Analysis)
Meta-Analysis
The benefit associated with the incorporation of vincristine-corticosteroid pulses in maintenance therapy for pediatric acute lymphoblastic leukemia (ALL) is unclear, particularly in the context of modern intensive therapy. This systematic review and meta-analysis examined the impact of reducing the frequency of vincristine-steroid pulses during maintenance for pediatric patients newly diagnosed with B-cell ALL. Two authors reviewed all eligible studies identified through a comprehensive search, extracted data from 25 publications (12 513 patients), and assessed the risk of bias. We created historical and contemporary subgroups; the latter included trials providing both a version of Protocol III from the early Berlin-Frankfurt-Munster trials and eliminating routine prophylactic cranial radiation. Meta-analysis of event-free survival data suggested no benefit between more frequent or less frequent pulses in contemporary trials (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.85-1.09), which differed significantly from historical trials (HR, 0.79; 95% CI, 0.68-0.91; P = .04). We found no significant impact of reduced pulse frequency on overall survival or relapse risk. There was however increased odds of grade 3+ nonhepatic toxicity in the high-pulse frequency group (odds ratio, 1.31; 95% CI, 1.12-1.52). This systematic review suggests that the previous benefit conferred by frequent pulses of vincristine-steroids in maintenance therapy for pediatric B-cell ALL in historical trials no longer applies in contemporary trials but is associated with toxicity. These results will help guide the development of the next phase of clinical trials in the field of pediatric ALL and question the continued use of pulses in maintenance among patients not in clinical trials, particularly those experiencing toxicity.
Topics: Humans; Child; Vincristine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Adrenal Cortex Hormones; Steroids; Progression-Free Survival; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 36821772
DOI: 10.1182/blood.2022018899 -
Cancer Gene Therapy Jun 2023Chimeric Antigen Receptor (CAR) T cell therapy is an effective treatment approach for patients with relapsed or refractory acute lymphoblastic leukemia (R/R B-ALL).... (Meta-Analysis)
Meta-Analysis
Long-term response to autologous anti-CD19 chimeric antigen receptor T cells in relapsed or refractory B cell acute lymphoblastic leukemia: a systematic review and meta-analysis.
Chimeric Antigen Receptor (CAR) T cell therapy is an effective treatment approach for patients with relapsed or refractory acute lymphoblastic leukemia (R/R B-ALL). However, identifying the factors that influence long-term response to this therapy is necessary to optimize patient selection and treatment allocation. We conducted a literature review and meta-analysis to investigate the use of autologous anti-CD19 CAR T cell therapy in both pediatric and adult patients with R/R B-ALL, using several databases including MEDLINE, Cochrane Central, ScienceDirect, Web of Science, Journals@Ovid, Embase, and clinicaltrial.gov. A total of 38 reports were analyzed, which enrolled 2134 patients. Time-to-event endpoints were estimated using reconstructed patient survival data. The study explored key modulators of response, including costimulatory domains, disease status, age, and lymphodepletion. The median overall survival and event-free survival were 36.2 months [95% CI 28.9, NR] and 13.3 months [95% CI 12.2, 17], respectively. The overall response rate was 76% [95% CI 71, 81]. The use of 4-1BB costimulatory domain in the CAR construct, administration of low-dose cyclophosphamide lymphodepletion, and pretreatment morphologic remission were associated with better overall survival, with hazard ratios of 0.72, 0.56, and 0.66, respectively. Morphologic remission and 4-1BB domain were associated with better event-free survival, with hazard ratios of 0.66 and 0.72, respectively. These findings suggest that CAR T cell therapy may offer long-term benefits to patients with R/R B-ALL. However, further research is needed to optimize patient selection and better understand the impact of various factors on the outcome of CAR T cell therapy.
Topics: Adult; Humans; Child; Receptors, Chimeric Antigen; Receptors, Antigen, T-Cell; Immunotherapy, Adoptive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; T-Lymphocytes
PubMed: 36750666
DOI: 10.1038/s41417-023-00593-3 -
Clinical Lymphoma, Myeloma & Leukemia Apr 2023Allogeneic hematopoietic stem cell transplant (HSCT) is indicated in pediatric patients with acute lymphoblastic leukemia (ALL) who have relapsed or are at a very high... (Meta-Analysis)
Meta-Analysis Review
Total Body Irradiation Versus Chemotherapy Conditioning in Pediatric Acute Lymphoblastic Leukemia Patients Undergoing Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis.
Allogeneic hematopoietic stem cell transplant (HSCT) is indicated in pediatric patients with acute lymphoblastic leukemia (ALL) who have relapsed or are at a very high risk of relapse during first complete remission. Two types of myeloablative conditioning are employed before allogeneic HSCT: total body irradiation (TBI)-based regimens and chemotherapy (CHT) alone. This study compares the efficacy and safety of TBI-based regimens and CHT-based conditioning in pediatric, adolescent, and young adult patients with ALL (0-24 years old). TBI-based and CHT-conditioning regimens were evaluated in 4262 and 1367 patients, respectively, from 15 studies. Compared to CHT alone, TBI-based regimens were associated with better overall survival (OS), relative risk (RR) 1.21, better event-free survival (RR 1.34), and a reduced risk of relapse (RR 0.69). Both approaches had comparable risk of acute graft-versus-host disease (GVHD), grades 3 to 4 acute GVHD, chronic GVHD, and nonrelapse mortality (NRM). In the subgroup analysis for patients in first complete remission, TBI-based regimens and CHT alone had comparable OS and NRM. Our results demonstrate the superiority of TBI-based regimens compared to CHT alone in pediatric patients with ALL.
Topics: Adolescent; Young Adult; Humans; Child; Infant, Newborn; Infant; Child, Preschool; Adult; Whole-Body Irradiation; Busulfan; Transplantation, Homologous; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; Recurrence; Retrospective Studies
PubMed: 36725384
DOI: 10.1016/j.clml.2023.01.004 -
Clinical Lymphoma, Myeloma & Leukemia Mar 2023We conducted a systematic review and meta-analysis to compare outcomes of tyrosine kinase inhibitor (TKI) maintenance therapy with or without allogeneic hematopoietic... (Meta-Analysis)
Meta-Analysis Review
Outcomes of Tyrosine Kinase Inhibitors Maintenance Therapy with or without Allogeneic Hematopoietic Stem Cell Transplantation in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in First Complete Remission: A Systematic Review and Meta-Analysis.
We conducted a systematic review and meta-analysis to compare outcomes of tyrosine kinase inhibitor (TKI) maintenance therapy with or without allogeneic hematopoietic stem cell transplantation (HSCT) in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in first remission (CR1). A literature search was performed on PubMed, Cochrane, and Clinical trials.gov. After screening 1720 articles, 12 studies were included. Proportions and odds ratios (OR) with 95% confidence intervals (CI) were computed. I provides an estimate of the percentage of variability in results across studies that is due to real differences and not due to chance. Of 1039 patients, 635 (61%) had TKI alone and 404 (39%) patients had HSCT followed by TKI. At 3 years, a trend towards poor overall survival (OS; OR 0.67, 95% CI 0.39-1.15, I = 68%), (disease-free survival; OR 0.58, 95% CI 0.26-1.29, I = 76%), and higher relapse rate (RR; OR = 2.52, 95% CI = 1.66-3.83, I = 26%) was seen with TKI alone compared to HSCT-TKI. Although HSCT followed by TKI maintenance in Ph+ ALL has long been considered standard of care, the introduction of potent third-generation TKIs and bispecific T-cell engagers such as Blinatumomab has significantly improved outcomes while sparing the need for HSCT in newly diagnosed patients.
Topics: Humans; Tyrosine Kinase Inhibitors; Philadelphia Chromosome; Remission Induction; Hematopoietic Stem Cell Transplantation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Kinase Inhibitors
PubMed: 36682989
DOI: 10.1016/j.clml.2023.01.002 -
Current Oncology (Toronto, Ont.) Jan 2023Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and young adults. Treatment is long and involves 2-3 years of a prolonged maintenance phase... (Review)
Review
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and young adults. Treatment is long and involves 2-3 years of a prolonged maintenance phase composed of oral chemotherapies. Adherence to these medications is critical to achieving good outcomes. However, adherence is difficult to determine, as there is currently no consensus on measures of adherence or criteria to determine nonadherence. Furthermore, there have been few studies in pediatric B-ALL describing factors associated with nonadherence. Thus, we performed a systematic review of literature on oral chemotherapy adherence during maintenance therapy in ALL following PRISMA guidelines. Published studies demonstrated various objective and subjective methods of assessing adherence without generalizable definitions of nonadherence. However, the results of these studies suggested that nonadherence to oral maintenance chemotherapy was associated with increased risk of relapse. Future studies of B-ALL therapy should utilize a uniform assessment of adherence and definitions of nonadherence to better determine the impact of nonadherence on B-ALL outcomes and identify predictors of nonadherence that could yield targets for adherence improving interventions.
Topics: Child; Humans; Adolescent; Young Adult; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Administration, Oral; Recurrence
PubMed: 36661705
DOI: 10.3390/curroncol30010056 -
Clinical Lymphoma, Myeloma & Leukemia Mar 2023The aim was to evaluate the efficacy and safety of blinatumomab monotherapy for the treatment of relapsed/refractory acute lymphoblastic leukemia (R/R B-ALL). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim was to evaluate the efficacy and safety of blinatumomab monotherapy for the treatment of relapsed/refractory acute lymphoblastic leukemia (R/R B-ALL).
METHODS
PubMed, Embase, Web of Science, and Cochrane Library were searched to collect clinical studies related to blinatumomab. The primary outcome measures were complete remission (CR), and minimal residual disease (MRD) response. Prognostic indicators included overall survival (OS) and relapse-free survival time (RFS). Grade ≥3 adverse reactions were mainly analyzed for safety, including cytokine release syndrome (CRS), neurological events and hematological toxicity. The heterogeneity was quantified by I statistic, which reflected the proportion of the true heterogeneity to the variance of the total effect size. Studies were considered heterogeneous if the I statistic was greater than 50%, and conversely, studies were homogeneous.
RESULTS
A total of 18 studies involving 1,373 patients were included. The analysis results showed a CR rate of 54% (95%CI:44%-64%) and an MRD response rate of 43% (95%CI:34%-51%). The CR rate was higher in patients with bone marrow (BM) blast <50% than in patients with BM blast ≥50% (71% vs. 34%). The median OS and RFS were 8.16 months (95%CI:6.64-9.69) and 6.02 months (95%CI:4.63-7.41), respectively. For safety analysis, the incidence of grade ≥3 adverse events (AEs) was 80% (95%CI:72%-88%), the incidence of grade ≥3 neurological toxicity was 7% (95%CI:4%-11%), and the incidence of grade ≥3 CRS was 3% (95%CI:2%-5%). However, the mixture of retrospective and prospective studies led to heterogeneity to some extent in this meta-analysis.
CONCLUSION
Blinatumomab is effective in the treatment of R/R B-ALL with a controlled occurrence of AEs and a reliable safety profile.
Topics: Humans; Antibodies, Bispecific; Leukemia, Lymphoid; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Recurrence; Retrospective Studies
PubMed: 36593170
DOI: 10.1016/j.clml.2022.12.009 -
Mayo Clinic Proceedings Jan 2023To examine the risk of hematologic malignancies in older adults with ankylosing spondylitis (AS).
OBJECTIVE
To examine the risk of hematologic malignancies in older adults with ankylosing spondylitis (AS).
PATIENTS AND METHODS
We used US Medicare data from January 1, 1999, to December 31, 2010, to identify a population-based cohort of beneficiaries with AS. We also included beneficiaries with inflammatory bowel disease (IBD) as disease controls and beneficiaries without AS or IBD as unaffected controls. We excluded those treated with tumor necrosis factor inhibitors in this period. We followed up each group for new diagnosis claims for hematologic malignancies until September 30, 2015.
RESULTS
We included 12,451 beneficiaries with AS, 234,905 with IBD, and 10,975,340 unaffected controls, with a mean follow-up of 9.9, 9.3, and 8.0 years, respectively. We identified 297 hematologic malignancies in the AS group, 4538 malignancies in the IBD group, and 128,239 malignancies in unaffected controls. The standardized incidence ratio in AS vs unaffected controls was 1.39 (95% CI, 1.05 to 1.61) for non-Hodgkin lymphoma, 1.50 (95% CI, 1.17 to 1.92) for chronic lymphocytic leukemia, and 1.52 (95% CI, 1.12 to 2.06) for multiple myeloma. Risks of acute myeloid leukemia and chronic myeloid leukemia were not elevated in AS, and there were too few cases of Hodgkin lymphoma to compute risks. Risks were comparable to those of beneficiaries with IBD. We also performed a systematic literature review of the risk of hematologic malignancy in AS, focusing on age associations, which have not been previously examined. We identified 21 studies in the systematic literature review, which included mainly young or middle-aged patients. Results suggested that AS was largely not associated with an increased risk of hematologic malignancies. Two cohort studies reported an increased risk of multiple myeloma in AS.
CONCLUSION
The risks of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma are increased among elderly patients with AS.
Topics: Middle Aged; Humans; Aged; United States; Multiple Myeloma; Cohort Studies; Leukemia, Lymphocytic, Chronic, B-Cell; Spondylitis, Ankylosing; Medicare; Hematologic Neoplasms; Lymphoma, Non-Hodgkin; Inflammatory Bowel Diseases
PubMed: 36470752
DOI: 10.1016/j.mayocp.2022.06.030 -
Clinical Rheumatology Feb 2023Osteoarticular manifestations such as arthritis and bone pain are scarce among adults with acute lymphoblastic leukemia (ALL). We present a systematic review of... (Review)
Review
Osteoarticular manifestations such as arthritis and bone pain are scarce among adults with acute lymphoblastic leukemia (ALL). We present a systematic review of osteoarticular first clinical manifestation related to ALL in adults, and we report a case of an adult patient with a B-cell ALL revealed by refractory pygalgia and arthritis. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the MEDLINE database, including case reports and case series describing osteoarticular manifestations revealing ALL in adults. There were 29 patients with osteoarticular manifestations, revealing ALL (including our case). The mean age was 34.00 ± 13.29 years. Osteoarticular manifestations were peripheral articular signs (7 cases), axial manifestations (17 cases), and osteolytic lesions (21 cases). Vertebral fractures were reported in 4 cases. MRI was performed in 15 cases, showing heterogeneous signal changes in the vertebra, skull, and sacroiliac bones. It showed avascular necrosis of the femoral head in one case. PET scan, performed in 7 cases, showed diffuse or localized FDG uptakes in the bone marrow. Hypercalcemia was noted in 9 cases. The treatment was based on chemotherapy (23 patients) and radiotherapy (4 cases). During the follow-up, remission was noted in 14 cases, death in 9 cases, and was not available in 6 patients. Our review showed that axial manifestations, joint swelling, bone pain, and hypercalcemia could be the first and only symptoms of ALL in adults, making the diagnosis of ALL difficult to recognize, leading to a diagnosis delay. Key Points • Acute lymphoblastic leukemia in adults revealed by osteoarticular manifestations can be misdiagnosed as rheumatic diseases. • Axial manifestations, joint swelling, bone pain, and hypercalcemia could be the first and only symptoms of acute lymphoblastic leukemia in adults. • Complete blood count and calcium blood test should be performed as first-line investigations in adults with axial or peripheral articular symptoms. • Physicians should be aware of this clinical presentation to avoid diagnosis delay and improve prognosis.
Topics: Humans; Adult; Young Adult; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Arthritis; Joint Diseases; Bone Diseases; Acute Disease; Pain
PubMed: 36454343
DOI: 10.1007/s10067-022-06459-7 -
Annals of Hematology Jan 2023The complete remission (CR) rate and overall survival (OS) of relapsed/refractory (R/R) B-cell acute lymphoblastic leukaemia (B-ALL) are not satisfactory. The available... (Meta-Analysis)
Meta-Analysis
The complete remission (CR) rate and overall survival (OS) of relapsed/refractory (R/R) B-cell acute lymphoblastic leukaemia (B-ALL) are not satisfactory. The available salvage regimens include standard chemotherapy, inotuzumab ozogamicin, blinatumomab and cluster of differentiation (CD)19 chimeric antigen receptor T cells (CAR T), and the NCCN guidelines recommend all of these therapies with no preference. Dual CD19/CD22 CAR T-cells have emerged as new treatments and have shown some efficacy, with high CR rates and preventing CD19-negative relapse. However, direct comparisons of the CR rate and long-term survival among the different salvage therapies are lacking. Databases including PubMed, Embase, Web of Science and Cochrane were searched from inception to January 31, 2022, for relevant studies. The outcomes of interest were complete remission/complete remission with incomplete haematologic recovery (CR/CRi) rates and 1-year overall survival (OS) rates. Odds ratios (ORs) were generated for binary outcomes, and the mean difference (MD) was generated for consecutive outcomes by network meta-analysis. CD19 CAR T-cells demonstrated a significantly better effect in improving the CR/CRi rate than blinatumomab (OR = 8.32, 95% CI: 1.18 to 58.44) and chemotherapy (OR = 16.4, 95% CI: 2.76 to 97.45). In terms of OS, CD19 CAR T-cells and dual CD19/CD22 CAR T-cells both had a higher 1-year OS rate than blinatumomab, inotuzumab ozogamicin and chemotherapy. There was no significant difference between CD19 CAR T-cells and dual CD19/CD22 CAR T-cells in terms of 1-year OS and CR/CRi rates. CD19 CAR T-cells are effective in inducing CR, and CD19 CAR T-cells and dual CD19/CD22 CAR T-cells show benefits for overall survival. More high-quality randomized controlled trials and longer follow-ups are needed to confirm and update the results of this analysis in the future.
Topics: Humans; Inotuzumab Ozogamicin; Network Meta-Analysis; Neoplasm Recurrence, Local; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Antigens, CD19
PubMed: 36394582
DOI: 10.1007/s00277-022-05040-1