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Hematology/oncology and Stem Cell... Jun 2019Cutaneous immunoglobulin (Ig) amyloid light-chain (AL) amyloidosis associated with overt multiple myeloma (MM) is rare and optimal treatment is not well defined. The...
OBJECTIVE/BACKGROUND
Cutaneous immunoglobulin (Ig) amyloid light-chain (AL) amyloidosis associated with overt multiple myeloma (MM) is rare and optimal treatment is not well defined. The recently developed highly efficacious MM therapy has brought on a new set of challenges to this field for consideration. The goal of this paper is to describe the characteristics of cutaneous manifestations of systemic AL amyloidosis associated with MM according to age, sex, race, Ig type, plasma cell percentage, and cytogenetic and fluorescent in situ hybridization studies along with their outcomes.
METHODS
An electronic search of the PubMed database was performed to obtain key literature in AL amyloidosis and MM, using the following search terms: multiple myeloma, immunoglobulin light chain amyloidosis, and cutaneous amyloidosis. The search results were narrowed by selecting studies in English. Results were confined to the following articles types: case reports, case series, and systematic reviews.
RESULTS
We identified 32 cases from the PubMed database search and examined their potential relevance. We found the following: (a) higher prevalence in women (two-thirds) and white population; (b) IgG and IgA were equally distributed with lambda (λ) light chain occurring in 53-66% of cases; (c) majority of cases (56%) presented as hemorrhagic bullous lesions, followed by purpura/ecchymosis in 25% of cases; and (d) majority (64%) died within 6 months since diagnosis.
CONCLUSIONS
We reviewed the constellation of the cutaneous manifestations of AL amyloidosis with concurrent MM. We found a female predominance, and more than half presented as hemorrhagic bullous lesions. There is a preponderance of λ light chains over kappa (κ) light chains, both as a free light chain (15% vs. 4%) and as an intact Ig (38% vs. 24%; absolute number of 14 vs. 7 patients, respectively). In the subgroup of patients with bullous skin lesions, λ light chain was present in eight cases and κ light chain in seven cases. All κ light chain subtypes presented with bullous lesions and no other cutaneous types of lesions. They carried very poor prognosis with majority of cases surviving only 6 months, much worse than overall patients with AL amyloidosis without myeloma or myeloma without amyloidosis.
Topics: Adult; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Multiple Myeloma; Neoplasm Proteins; Sex Factors; Skin Neoplasms
PubMed: 30261180
DOI: 10.1016/j.hemonc.2018.09.003 -
Annals of Oncology : Official Journal... Apr 2019To summarise the evidence on the associations between body mass index (BMI) and BMI in early adulthood, height, waist circumference (WC) and waist-to-hip ratio (WHR),... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To summarise the evidence on the associations between body mass index (BMI) and BMI in early adulthood, height, waist circumference (WC) and waist-to-hip ratio (WHR), and risk of lympho-haematopoietic cancers.
METHOD
We conducted a meta-analysis of prospective studies and identified relevant studies published up to December 2017 by searching PubMed. A random-effects model was used to calculate dose-response summary relative risks (RRs).
RESULTS
Our findings showed BMI, and BMI in early adulthood (aged 18-21 years) is associated with the risk of Hodgkin's and non-Hodgkin's lymphoma (HL and NHL), diffuse large beta-cell lymphoma (DLBCL), Leukaemia including acute and chronic myeloid lymphoma (AML and CML), and chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). The summary RR per 5 kg/m2 increase in BMI were 1.12 [95% confidence interval (CI): 1.05-1.20] for HL, 1.05 (95% CI: 1.03-1.08) for NHL, 1.11 (95% CI: 1.05-1.16) for DLBCL, 1.06 (95% CI: 1.03-1.09) for ML, 1.09 (95% CI: 1.03-1.15) for leukaemia, 1.13 (95% CI: 1.04-1.24) for AML, 1.13 (95% CI: 1.05-1.22) for CML and 1.04 (95% CI: 1.00-1.09) for CLL, and were1.12 (95% CI: 1.05-1.19) for NHL, 1.22 (95% CI: 1.09-1.37) for DLBCL, and 1.19 (95% CI: 1.03-1.38) for FL for BMI in early adulthood analysis. Results on mortality showed a 15%, 16% and 17% increased risk of NHL, MM and leukaemia, respectively. Greater height increased the risk of NHL by 7%, DLBCL by 10%, FL by 9%, MM by 5% and Leukaemia by 7%. WHR was associated with increased risk of DLBCL by 12%. No association was found between higher WC and risk of MM.
CONCLUSION
Our results revealed that general adiposity in adulthood and early adulthood, and greater height may increase the risk of almost all types of lympho-haematopoietic cancers and this adds to a growing body of evidence linking body fatness to several types of cancers.
Topics: Adiposity; Body Mass Index; Body Size; Humans; Leukemia; Lymphoma; Multiple Myeloma; Obesity; Risk Assessment; Risk Factors
PubMed: 30753270
DOI: 10.1093/annonc/mdz045 -
PloS One 2021Immunoproliferative Small Intestinal Disease (IPSID) is a disease characterized by extra-nodal marginal zone B-cell lymphoma with villous atrophy in the small intestine,...
Immunoproliferative Small Intestinal Disease (IPSID) is a disease characterized by extra-nodal marginal zone B-cell lymphoma with villous atrophy in the small intestine, causing chronic intermittent non-bloody diarrhea. Although originally associated with the Mediterranean region, this disease is present in many countries worldwide and may have been underreported due to its complicated diagnosis and scarce scientific literature, especially in regards to treatment. This study aims to review IPSID clinical features, therapeutic options, and treatment outcomes to help physicians identify and treat IPSID. Using PRISMA guidelines, a systematic review of articles was conducted on PubMed database with search terms including IPSID, therapy, treatment, and outcomes. Inclusion and exclusion criteria were used to select 33 English language articles published from the year 2000-2020 that included relevant clinical information about IPSID treatment. Data were extracted independently by at least two authors to reduce the introduction of potential bias. There were 22 case reports, 7 reviews, 1 research article, 1 prospective study, 1 letter to the editor and 1 memoriam in which 76 patients were identified. Epidemiological analysis showed a mean patient age of 32 years old, 2.4:1 mal to female ratio and heterogeneous ethnicities, with 16 Europeans (43.2%) and 12 Asians (32.4%). Chief symptoms included chronic diarrhea (53/76, 69.7%), weight loss (49/76, 64.4%), malabsorption (38/76, 50%), abdominal pain (32/76, 42.1%), and finger clubbing (24/76, 31.6%). Patients stratified into the early disease stage (Galian A) were treated with tetracycline antibiotics, corticosteroids, and non-pharmacological supplements with mostly with complete or partial remission. Late stages (Galian B or C), were treated mostly with anthracycline-based chemotherapy, and occasionally surgery, radiotherapy, or rituximab. This work offers a targeted approach to diagnosing and treating IPSID to aid physicians and serve as a treatment guideline recommendation for future public policies and clinical studies.
Topics: Adult; Anti-Bacterial Agents; Diarrhea; Humans; Immunoproliferative Small Intestinal Disease
PubMed: 34270561
DOI: 10.1371/journal.pone.0253695 -
Pituitary Jun 2017Parasellar plasmacytomas are rare tumors localized to the sellar region arising from plasma cells. Knowledge of clinical, imaging, surgical, and pathological... (Review)
Review
PURPOSE
Parasellar plasmacytomas are rare tumors localized to the sellar region arising from plasma cells. Knowledge of clinical, imaging, surgical, and pathological characteristics is limited to single case reports.
METHODS
A retrospective analysis of five primary cases was conducted, followed by systematic review of English language articles using PubMed in accordance with PRISMA guidelines.
RESULTS
Five primary case patients include four men and one woman, ages 60-77, followed up to 3 years. A systematic review identified 65 additional patients, of whom 65% presented with cranial nerve palsies and 15% with hypopituitarism. Sixteen percent had history of known multiple myeloma (MM) while 37% were diagnosed concurrently with MM on presentation of parasellar plasmacytoma. Imaging showed median tumor size of 38 mm (range, 4-70 mm), with MRI intensity similar to that of other sellar masses. Surgical biopsy with immunohistochemical studies confirmed plasmacytoma diagnosis. Eighty-one percent underwent parasellar radiotherapy, and chemotherapy initiated in 59% of the 69 patients with MM. Overall survival rate was 74% at follow-up (median 12 months), with 18% having parasellar recurrences and 38% progressing to systemic MM after presentation of a solitary plasmacytoma (median 3 months).
CONCLUSIONS
Parasellar plasmacytomas are rare tumors that should be considered in the differential diagnosis for lesions involving the sella and arising from the clivus, especially when cranial nerve paresis is apparent, even in the absence of known MM. Although recurrence rates for parasellar plasmacytoma is low, patients should be monitored for progression to MM. Treatment depends on the presence of systemic disease at diagnosis.
Topics: Aged; Female; Humans; Male; Multiple Myeloma; Plasmacytoma; Retrospective Studies
PubMed: 28251542
DOI: 10.1007/s11102-017-0799-5 -
Medicine Nov 2016Renal insufficiency is a common and severe complication of patients with multiple myeloma. The aim of this study was to evaluate bortezomib-based treatment for multiple... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Renal insufficiency is a common and severe complication of patients with multiple myeloma. The aim of this study was to evaluate bortezomib-based treatment for multiple myeloma patients with renal insufficiency.
METHODS
The Cochrane Library, Embase, PubMed, ISI, China National Knowledge Infrastructure, Chinese Biomedical Literature Service System, Chongqing VIP Database, and Wan Fang Data were systematically searched to identify observational studies from January 1, 2001, to December 31, 2015. Myeloma response rate and renal remission rate were pooled by using risk ratio and 95% confidence interval (CI). The Cochran Q and I statistics were used to assess heterogeneity. Sensitivity analysis was performed to test the feasibility of pooled results. Publication bias was conducted when included studies were ≥9. Furthermore, grades of evidence were performed to evaluate study quality.
RESULTS
Eleven retrospective cohort studies were included in the final analysis. The number of available studies and risk ratios (95% CI) were, respectively, 10 and 1.48 (95% CI: 1.28-1.71) for myeloma overall response, 6 and 3.69 (95% CI: 2.22-6.13) for myeloma complete response, 9 and 1.47 (95% CI: 1.28-1.69) for renal overall remission, and 8 and 1.49 (95% CI: 1.26-1.75) for renal complete remission. No significant publication bias was observed and sensitivity analysis confirmed the stability of results. The overall qualities of evidence were high for myeloma complete response and medium for the other 3 outcomes based on the Grading of Recommendations, Assessment, Development and Evaluation system.
CONCLUSION
Current evidence indicated that bortezomib-based treatment could improve myeloma overall response (especially myeloma complete response) and renal overall remission (including renal complete remission).
Topics: Antineoplastic Agents; Bortezomib; Humans; Multiple Myeloma; Observational Studies as Topic; Remission Induction; Renal Insufficiency
PubMed: 27861343
DOI: 10.1097/MD.0000000000005202 -
The Cochrane Database of Systematic... Oct 2015Autologous stem cell transplantation is widely used to restore functioning bone marrow in people with malignant lymphoma or multiple myeloma after myeloablative... (Meta-Analysis)
Meta-Analysis Review
Additional plerixafor to granulocyte colony-stimulating factors for haematopoietic stem cell mobilisation for autologous transplantation in people with malignant lymphoma or multiple myeloma.
BACKGROUND
Autologous stem cell transplantation is widely used to restore functioning bone marrow in people with malignant lymphoma or multiple myeloma after myeloablative chemotherapy. Results of some clinical trials indicate that plerixafor in addition to granulocyte colony-stimulating factors (G-CSF) compared to G-CSF only could lead to an increased mobilisation and release of CD34-positive cells, facilitating effective apheresis.
OBJECTIVES
To evaluate the efficacy and safety of additional plerixafor to G-CSF for haematopoietic stem cell mobilisation in people with malignant lymphoma or multiple myeloma.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1990 to September 2015), as well as conference proceedings (American Society of Hematology; American Society of Clinical Oncology; European Hematology Association; American Society for Blood and Marrow Transplantation; European Group for Blood and Marrow Transplantation) for studies. Two review authors independently screened search results.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing plerixafor in addition to G-CSF compared to G-CSF only for stem cell mobilisation in people with malignant lymphoma or multiple myeloma of all stages and ages. We included full text as well as abstracts and unpublished data if sufficient information on study design, participant characteristics, interventions, and outcomes was available. We excluded cross-over trials, quasi-randomised trials, and post-hoc retrospective trials.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the results of the search strategies, extracted data, assessed quality, and analysed data according to standard Cochrane methods. We performed final interpretation with an experienced clinician.
MAIN RESULTS
We identified four RCTs fitting the inclusion criteria. However, two of these closed prematurely due to low recruitment and did not report results. The remaining two trials evaluated 600 participants with multiple myeloma or non-Hodgkin lymphoma. In both studies the experimental group received G-CSF plus plerixafor and the control group received G-CSF plus placebo.The meta-analysis showed no evidence for differences between plerixafor and placebo group regarding mortality at 12 months (600 participants; risk ratio (RR) 1.00, 95% confidence interval (CI) 0.59 to 1.69; P = 1.00; moderate-quality evidence) and adverse events during stem cell mobilisation and collection (593 participants; RR 1.02, 95% CI 0.99 to 1.06; P = 0.19; high-quality evidence).Regarding the outcome successful stem cell collection, the meta-analysis showed an advantage for those participants randomised to the plerixafor group (600 participants; RR 2.42, 95% CI 1.98 to 2.96; P < 0.00001; high-quality evidence).As there was high heterogeneity between studies for the number of transplanted participants, we did not meta-analyse these data. In the multiple myeloma study, 95.9% (142 participants) in the plerixafor arm and 88.3% (136 participants) in the placebo arm underwent transplantation (RR 1.09, 95% CI 1.02 to 1.16); in the non-Hodgkin lymphoma trial, 90% (135 participants) in the plerixafor group versus 55.4% (82 participants) in the placebo group could be transplanted (RR 1.62, 95% CI 1.39 to 1.89). In both trials there was no evidence for a difference between participants in the plerixafor and placebo group in terms of time to neutrophil and platelet engraftment in transplanted participants.None of the trials reported on the outcomes quality of life and progression-free survival.
AUTHORS' CONCLUSIONS
The results of the analysed data suggest that additional plerixafor leads to increased stem cell collection in a shorter time. There was insufficient evidence to determine whether additional plerixafor affects survival or adverse events.The two trials included in the meta-analysis, both of which were conducted by the Genzyme Corporation, the manufacturer of plerixafor, were published several times. Two more RCTs examining the addition of plerixafor to a G-CSF mobilisation regimen terminated early without publishing any outcome. The trials included nine and five participants, respectively. Another RCT with 100 participants was recently completed, but has not yet published outcomes. Due to the unpublished RCTs, it is possible that our review is affected by publication bias, even though two trials failed to recruit a sufficient number of participants to analyse any data.
Topics: Benzylamines; Cyclams; Early Termination of Clinical Trials; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Heterocyclic Compounds; Humans; Lymphoma; Lymphoma, Non-Hodgkin; Multiple Myeloma; Randomized Controlled Trials as Topic; Time Factors; Transplantation, Autologous
PubMed: 26484982
DOI: 10.1002/14651858.CD010615.pub2 -
European Radiology Feb 2018Many radiologists and clinicians still consider multiple myeloma (MM) and monoclonal gammopathies (MG) a contraindication for using iodine-based contrast media. The ESUR... (Review)
Review
OBJECTIVES
Many radiologists and clinicians still consider multiple myeloma (MM) and monoclonal gammopathies (MG) a contraindication for using iodine-based contrast media. The ESUR Contrast Media Safety Committee performed a systematic review of the incidence of post-contrast acute kidney injury (PC-AKI) in these patients.
METHODS
A systematic search in Medline and Scopus databases was performed for renal function deterioration studies in patients with MM or MG following administration of iodine-based contrast media. Data collection and analysis were performed according to the PRISMA statement 2009. Eligibility criteria and methods of analysis were specified in advance. Cohort and case-control studies reporting changes in renal function were included.
RESULTS
Thirteen studies were selected that reported 824 iodine-based contrast medium administrations in 642 patients with MM or MG, in which 12 unconfounded cases of PC-AKI were found (1.6 %). The majority of patients had intravenous urography with high osmolality ionic contrast media after preparatory dehydration and purgation.
CONCLUSIONS
MM and MG alone are not risk factors for PC-AKI. However, the risk of PC-AKI may become significant in dehydrated patients with impaired renal function. Hypercalcaemia may increase the risk of kidney damage, and should be corrected before contrast medium administration. Assessment for Bence-Jones proteinuria is not necessary.
KEY POINTS
• Monoclonal gammopathies including multiple myeloma are a large spectrum of disorders. • In monoclonal gammopathy with normal renal function, PC-AKI risk is not increased. • Renal function is often reduced in myeloma, increasing the risk of PC-AKI. • Correction of hypercalcaemia is necessary in myeloma before iodine-based contrast medium administration. • Bence-Jones proteinuria assessment in myeloma is unnecessary before iodine-based contrast medium administration.
Topics: Acute Kidney Injury; Contrast Media; Europe; Humans; Incidence; Iodine; Multiple Myeloma; Paraproteinemias; Radiology; Risk Factors; Societies, Medical
PubMed: 28856420
DOI: 10.1007/s00330-017-5023-5 -
Current Oncology (Toronto, Ont.) Mar 2023Inflammatory proteins activate platelets, which have been observed to be directly related to cancer progression and development. The aim of this systematic review is to... (Review)
Review
Inflammatory proteins activate platelets, which have been observed to be directly related to cancer progression and development. The aim of this systematic review is to investigate the possible association between Mean Platelet Volume (MPV) and cancer (diagnostic capacity of MPV, relation to survival, the severity of the disease, and metastasis). A literature review was performed in the online database PubMed and Google Scholar for the period of 2010-2022. In total, 83 studies including 21,034 participants with 12 different types of cancer (i.e., gastric cancer, colon cancer, esophageal squamous cell carcinoma, renal cancer, breast cancer, ovarian cancer, endometrial cancer, thyroid cancer, lung cancer, bladder cancer, gallbladder cancer, and multiple myeloma) were identified. The role of MPV has been extensively investigated in several types of cancer, such as gastric, colon, breast, and lung cancer, while few data exist for other types, such as renal, gallbladder cancer, and multiple myeloma. Most studies in gastric, breast, endometrium, thyroid, and lung cancer documented an elevated MPV in cancer patients. Data were less clear-cut for esophageal, ovarian, and colon cancer, while reduced MPV was observed in renal cell carcinoma and gallbladder cancer. Several studies on colon cancer (4 out of 6) and fewer on lung cancer (4 out of 10) indicated an unfavorable role of increased MPV regarding mortality. As far as other cancer types are concerned, fewer studies were conducted. MPV can be used as a potential biomarker in cancer diagnosis and could be a useful tool for the optimization of treatment strategies. Possible underlying mechanisms between cancer and MPV are discussed. However, further studies are needed to elucidate the exact role of MPV in cancer progression and metastasis.
Topics: Female; Humans; Mean Platelet Volume; Gallbladder Neoplasms; Esophageal Neoplasms; Multiple Myeloma; Esophageal Squamous Cell Carcinoma; Lung Neoplasms; Colonic Neoplasms
PubMed: 36975471
DOI: 10.3390/curroncol30030258 -
American Journal of Hematology Jul 2022Bruton tyrosine kinase inhibitors (BTKi) are important treatment options in Waldenström's macroglobulinemia (WM). Whether second-generation BTKi are associated with... (Meta-Analysis)
Meta-Analysis
Bruton tyrosine kinase inhibitors (BTKi) are important treatment options in Waldenström's macroglobulinemia (WM). Whether second-generation BTKi are associated with improved outcomes and/or better safety profile remains unclear. We did a systematic review and meta-analysis of clinical trials that reported data on the outcomes of patients with WM who received either first- or second-generation BTKi in the period between January 2010 and August 2021. Studies with twenty or fewer patients were excluded. The primary outcomes were efficacy measured by response and survival data. Eleven studies met the eligibility criteria and were included in the final analysis (n = 730 patients). A total of 298 patients received 1st-generation BTKi and 432 received a 2nd-generation BTKi. Pooled overall response rate (ORR) and major response rate (MRR) for both generations were similar (94.2% and 78.5% in 1st vs. 88.9% and 75.1% in 2nd, respectively). MRR for both generations was higher in MYD88 Mut/CXCR4 WT patients compared to MYD88 Mut/CXCR4 Mut patients (odds ratio [OR]: 3.9, 95% CI: 2.2 to 5.5). Pooled 18-mo progression-free survival (PFS) was similar for both generations (88.5% vs. 87.3%). Grade 3/4 atrial fibrillation was higher in 1st-generation BTKi (3.1% vs. 0.4%); however, grade-3/-4 infections and neutropenia were more frequent in 2nd-generarion BTKi (20.9% vs. 13.2%, 17.7% vs. 12%, respectively). The efficacy of 1st- and 2nd-generation BTKis is comparable. The 1st-generation BTKi were associated with a higher risk of atrial fibrillation, whereas infections and neutropenia occurred more frequently in 2nd-generation BTKi.
Topics: Atrial Fibrillation; Humans; Lymphoma, B-Cell; Mutation; Myeloid Differentiation Factor 88; Neutropenia; Protein Kinase Inhibitors; Pyrimidines; Waldenstrom Macroglobulinemia
PubMed: 35358350
DOI: 10.1002/ajh.26552 -
Critical Reviews in Oncology/hematology May 2018Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids.... (Review)
Review
Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%-23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone. Extensive literature search identified a total of 1839 articles. Twenty-six articles (n = 5980) met the inclusion criteria, 15 in newly diagnosed multiple myeloma (NDMM) and 11 in RRMM group. CFZ demonstrates comparable or even better efficacy to bortezomib with much favorable AE profile. Deep, rapid and sustainable response using KRd with safer toxicity profile supports extension of KRd therapy to frontline therapy for all risk categories of MM. High incidence of grade ≥3 HTN underscores the importance of serial BP monitoring. In RRMM, CFZ has documented efficacy with standard 20-27mg/m2 dose. Further large-scale trials are needed to study benefit-to-risk profile of 20-56 and 20-70 mg/m2 dose of CFZ vs standard 20-27 mg/m2 dose in NDMM and RRMM.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Drug Resistance, Neoplasm; Humans; Lenalidomide; Multiple Myeloma; Oligopeptides; Proteasome Inhibitors; Thalidomide; Treatment Outcome
PubMed: 29650268
DOI: 10.1016/j.critrevonc.2018.02.008