Infectious Complications in Patients With Multiple Myeloma After High-Dose Chemotherapy Followed by Autologous Stem Cell Transplant: Nationwide Study of the Infectious Complications Study Group of the Polish Adult Leukemia Group
Transplantation proceedings. 2020
BACKGROUND Multiple myeloma (MM) has become a chronic disease in majority of patients, and remission consolidation with autologous hematopoietic stem cell transplant (ASCT) remains the backbone of treatment in transplant-eligible patients. OBJECTIVE The aim of this multicenter cross-sectional nationwide retrospective study was to evaluate the epidemiology, etiology, and outcome of infections in patients with MM undergoing ASCT in 13 Polish transplant centers, carried out on behalf of the Infectious Complications Study Group of the Polish Adult Leukemia Group. METHODS A total number of consecutive 1374 patients with MM treated in Polish adult transplant centers from 2012 to 2014 were followed for infectious complications up to day +100 after ASCT in nationwide study. RESULTS Altogether 490 infection episodes in 336 patients (49% male, aged 21-72 years) were reported, including 145 episodes of neutropenic fever (103 patients) and 34 episodes of clinically documented infections (CDIs) (27 patients). Among microbiologically confirmed infections there were 251 episodes of bacterial infections (180 patients), 42 episodes of fungal infections (38 patients), and 18 episodes of viral infections (17 patients). The overall incidence of infections reached 13.1% for bacterial, 3.6% for fungal, and 1.3% for viral infections. There were 16 cases of infection-related deaths after ASCT (1.2%). The mortality risk factors included multidrug-resistant bacteria etiology (odds ratio [OR], 3.5; P = .033), coexistence of bacterial and fungal infection (OR, 6.3; P = .002), and CDI (OR, 5.5; P = .007). CONCLUSION ASCT in patients with MM was connected with low risk of life-threatening infections. However, multidrug-resistant bacteria bacterial etiology, mixed etiology, and CDI increased the risk of fatal outcome.
Presence of Parvovirus B19 but Not Herpesvirus Genome in Acute Skin Rash after Allogeneic Stem Cell Transplantation Correlates with Outcome
Acta haematologica. 2020;:1-10
INTRODUCTION Skin rash is a first symptom of acute graft-versus-host disease (GvHD) after allogeneic stem cell transplantation (ASCT) but can also be caused by viruses. The relevance of virus DNA analyses in skin rash for diagnosis and clinical outcome is unknown. OBJECTIVES To record the frequencies of detection of herpes and parvovirus B19 (ParvoB19) DNA in skin rash within 100 days after ASCT and to analyze their relevance for diagnosis, clinical course, and non-relapse mortality (NRM). METHODS We retrospectively identified 55 patients with virus DNA analysis for CMV, EBV, HHV6, HHV8, HSV, VZV, or ParvoB19. We assessed the rate of virus DNA detection and studied associations with histological diagnosis, virus DNA from concomitantly analyzed blood, clinical presentation, exanthema treatment, and NRM. RESULTS CMV, EBV, HHV6, HHV8, HSV, VZV and ParvoB19 DNA were detected in 12.5, 11.8, 10, 0, 0, 2.9, and 26.7% of exanthemas. Histopathological diagnosis was not associated with virus polymerase chain reaction (PCR) results. Detection of CMV, EBV, or HHV6 DNA but not ParvoB19 in skin and blood was associated with PCR results (p = 0.016; p < 0.001; p = 0.067; p = n.a.). Detection of CMV, EBV, HHV6, or ParvoB19 DNA in the skin was not significantly associated with patient, ASCT, or GvHD characteristics. Detection of ParvoB19 but not herpes virus DNA was associated with less immunosuppressive treatment (p = 0.015) and lower NRM (p = 0.041). In multivariate analyses, detection of ParvoB19 was associated with a lower NRM. CONCLUSIONS Detection of ParvoB19 DNA in exanthema after ASCT might be associated with lower NRM.
Red blood cell and platelet transfusion support in the first 30 and 100?days after allogeneic hematopoietic cell transplant
BACKGROUND Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients often require substantial but variable transfusion support. STUDY DESIGN AND METHODS This single-center, retrospective study evaluated the red blood cell (RBC) and platelet (PLT) transfusion data of first-time allo-HSCT recipients transplanted in 2011 to 2017. Multivariate analyses were performed to assess the associations between patient and transplant-related factors and transfusion requirements. RESULTS The study included 1762 patients who received peripheral blood stem cells (88.2%), marrow (7.0%), or umbilical cord (4.8%) from matched related (38.3%), unrelated (49.2%), or haploidentical (7.8%) donors. Almost all patients required RBCs (88.3%) or PLTs (97.4%) during the first 30?days, with medians of 3 (range, 1-37) RBC and 6 (range, 1-144) PLT units transfused. Fewer patients required RBC (43.8%) or PLT (27.3%) transfusions during Days 31 to 100, but the median (range) numbers of RBC and PLT units remained high at 3 (1-36) and 6 (1-116) among transfused patients. RBC and PLT transfusion independence was reached in medians of 24 (95% confidence interval [CI], 22-26) and 12 (95% CI, 11-12) days, respectively. Haploidentical donor, cord graft, and requiring RBC transfusions in the 10?days before HSCT were the most significant independent factors predictive of increased transfusion requirements. Advanced disease, diagnosis, ABO incompatibility, conditioning intensity, CD34+ cell dose, presence of severe acute graft-vs-host disease, and changes in recommended transfusion triggers were also shown to independently impact transfusion requirements. CONCLUSIONS This study provided for the first time quantitative and comparative transfusion data on a large contemporary cohort of HSCT recipients, including haploidentical and cord graft recipients, and identified factors predictive of increased transfusions.
Mesenchymal stem cell research progress for the treatment of COVID-19
J Int Med Res. 2020;48(9):300060520955063
At the end of 2019, novel coronavirus (COVID-19) infection was detected in Wuhan City, Hubei Province, China. The COVID-19 infection characteristics include a long incubation period, strong infectivity, and high fatality rate, and it negatively affects human health and social development. COVID-19 has become a common problem in the global medical and health system. It is essentially an acute self-limiting disease. Patients with severe COVID-19 infection usually progress to acute respiratory distress syndrome, sepsis, metabolic acidosis that is difficult to correct, coagulation dysfunction, multiple organ failure, and even death within a short period after onset. There remains a lack of effective drugs for such patients clinically. Mesenchymal stem cells (MSCs) are expected to reduce the risk of complications and death in patients because they have strong anti-inflammatory and immunomodulatory capabilities, which can improve the microenvironment, promote neovascularization, and enhance tissue repair capabilities. China is currently conducting several clinical trials on MSCs for the treatment of COVID-19. Here, we review the research progress related to using stem cells to treat patients with COVID-19.
Durable Survival Outcomes in Primary and Secondary Central Nervous System Lymphoma After High-dose Chemotherapy and Autologous Stem Cell Transplantation Using a Thiotepa, Busulfan, and Cyclophosphamide Conditioning Regimen
Clinical lymphoma, myeloma & leukemia. 2020
BACKGROUND High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been investigated in patients with primary central nervous system lymphoma (PCNSL) and non-Hodgkin lymphoma (NHL) with CNS involvement and has shown promising results. PATIENTS AND METHODS A retrospective analysis was performed of 48 consecutive patients who had undergone HDC/ASCT with TBC (thiotepa, busulfan, cyclophosphamide) conditioning for PCNSL (27 patients), secondary CNS lymphoma (SCNSL) (8 patients), or relapsed disease with CNS involvement (13 patients) from July 2006 to December 2017. Of the 27 patients with PCNSL, 21 had undergone ASCT at first complete remission (CR1). RESULTS The 2-year progression-free survival (PFS) rate was 80.5% (95% confidence interval [CI], 69.9-92.9) and the 2-year overall survival (OS) rate was 80.1% (95% CI, 69.2%-92.7%) among all patients. The 2-year PFS and OS rate for patients with PCNSL in CR1 was 95.2% (95% CI, 86.6%-100%) and 95.2% (95% CI, 86.6%-100%), respectively. On univariate analysis of the patients with PCNSL, ASCT in CR1 was the only variable statistically significant for outcome (P = .007 for PFS; P = .008 for OS). Among patients with SCNSL or CNS relapse, the 2-year PFS and OS rate were comparable at 75.9% (95% CI, 59.5%-96.8%) and 75.3% (95% CI, 58.6%-98.6%), respectively. The most common side effects were febrile neutropenia (89.6%; of which 66.7% had an infectious etiology identified), nausea/vomiting (85.4%), diarrhea (93.8%), mucositis (89.6%), and electrolyte abnormalities (89.6%). Four patients (8.3%) died of treatment-related overwhelming infection; of these patients, 3 had SCNSL. CONCLUSION HDC and ASCT using TBC conditioning for both PCNSL and secondary CNS NHL appears to have encouraging long-term efficacy with manageable side effects.
Vancomycin use and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation
Blood advances. 2020;4(12):2640-2643
Quality of Life following Allogeneic Stem Cell Transplantation for patients over 60 years with Acute Myeloid Leukaemia
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
This study of patients with acute myeloid leukemia (AML) aged ≥ 60 years analysed the association between patients' performance indices; haematopoietic stem cell transplantation comorbidity index (HCT-CI), Karnofsky Performance Score (KPS) and European Society for Blood and Marrow Transplantation (EBMT) risk score prior to allogeneic haematopoietic stem cell transplantation (allo-HSCT) and quality of life (QoL), quantified using the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT), in the first year post allo-HSCT. Over 7 years, 48 evaluable patients underwent reduced intensity conditioning (RIC) allo-HSCT. Median age was 65 years (range 60-74), with 2 year and 5 year overall survival (OS) of 65.8% and 52.3% respectively. A significant improvement across all QoL scores was observed over the 12 months post-HSCT. HCT-CI 0 was associated with improved general QoL (FACT-G) score at 6 months when compared with patients with HCT-CI 1-2 (p=0.032). At 12 months post-HSCT a higher HCT-CI ≥ 3 pre-transplant correlated with lower QoL scores across the domains (symptom related QoL (FACT-TOI), p=0.036; FACT-G, p=0.05; BMT-related QoL (FACT-BMT), p=0.036). Pre-transplant KPS 100 v 80-90 predicted for improved QoL at 6 months (FACT-TOI, p=0.009), FACT-G, p=0.001, FACT-BMT, p=0.002) but was not observed at one year post-HSCT. We demonstrate that KPS and HCT-CI can predict QoL in the early post-transplant period with a favourable overall survival in a selected cohort of AML patients over 60 years.
Prevalence and significance of sarcopenia in multiple myeloma patients undergoing autologous hematopoietic cell transplantation
Bone marrow transplantation. 2020
Sarcopenia, defined as loss of muscle mass, can occur with aging. We conducted a single-center retrospective analysis to evaluate the impact of muscle quality in multiple myeloma (MM), a hematologic cancer of older adults, undergoing autologous hematopoietic cell transplantation (autoHCT). Healthy muscle was quantified by measuring the percent of high-density muscle within the L3 psoas muscle using a novel computed tomography method in 142 eligible patients. Early post-transplant complications were assessed in the first 100 days after transplant. Sarcopenia, defined as =80% high-density muscle, was found in 72 (51%) patients. Sarcopenic obesity, defined as sarcopenia and a BMI?=?30, was found in 32 (23%) patients. One or more early complications occurred in 22 (16%) patients. Cardiovascular events accounted for 36% of all complications. Patients with sarcopenia had more cardiac complications (12.5%) than patients without (2.9%, p?=?0.03). Multivariate analysis revealed increased BMI at transplant, but not sarcopenia, was associated with worse OS (hazard ratio: 1.11, 95% confidence interval: 1.02-1.22, p?=?0.02). Our analysis suggests that sarcopenia is prevalent in MM and associated with increased early post-transplant cardiovascular complications in MM. Obesity, regardless of sarcopenia, is associated with worse survival in MM. Our study generates hypothesis-generating data to risk-stratify patients being considered for autoHCT.
Clinical trajectories, healthcare resource use, and costs of long-term hematopoietic stem cell transplantation survivors: a latent class analysis
Journal of cancer survivorship : research and practice. 2020
PURPOSE To identify patterns of healthcare utilization in allogeneic and autologous hematopoietic stem cell transplantation (HSCT) recipients and evaluate factors associated with high-need and high-cost post-transplantation care. METHODS Latent class analysis of a retrospective cohort of long-term allogeneic (n = 436) and autologous (n = 888) HSCT survivors within the Truven MarketScan database (2009-2014). We assessed factors associated with the latent classes by comparing post-transplantation healthcare utilization including inpatient admissions and length of stay, emergency room visits, specialist visits, and primary care provider visits. RESULTS Four utilization classes were identified in allogeneic and autologous HSCT recipients: (i) outpatient specialist care dominant (51.8% and 57.3%), (ii) outpatient primary care dominant (10.3% and 25.7%), (iii) outpatient/inpatient balanced (20.6% and 13.5%), and (iv) inpatient dominant (17.2% and 3.5%). Mean monthly healthcare expenditures in the inpatient dominant utilization class were $41,097 and $25,556 for allogeneic and autologous survivors, respectively, which were two to five times higher compared with other classes during the 2-year post-transplantation period. Factors associated with the high utilization class were transfusion (OR = 1.87, 95% CI 1.06-3.30) and 100-day post-transplant graft-versus-host-disease (OR = 1.76, 95% CI 1.05-2.94) in allogeneic HSCT; higher baseline Charlson comorbidity index (OR = 1.45, 95% CI 1.19-1.76) in autologous HSCT. CONCLUSION Based on distinct patterns of healthcare utilization following HSCT, we identified factors associated with higher resource utilization and greater healthcare related expenditures. IMPLICATIONS FOR CANCER SURVIVORS Earlier identification of high-cost and high-need HSCT long-term survivors could pave the way for clinicians to offer more continuous engagement in survivorship care delivery.
Mantle cell lymphoma relapsed after autologous stem cell transplantation: a single-center experience
Blood research. 2020;55(1):57-61
Background: Autologous stem cell transplantation (autoSCT) can extend remission of mantle cell lymphoma (MCL), but the management of subsequent relapse is challenging. Methods: We examined consecutive patients with MCL who underwent autoSCT at Veterans Affairs Puget Sound Health Care System between 2009 and 2017 (N=37). Results: Ten patients experienced disease progression after autoSCT and were included in this analysis. Median progression free survival after autoSCT was 1.8 years (range, 0.3-7.1) and median overall survival after progression was only 0.7 years (range, 0.1 to not reached). The 3 patients who survived more than 1 year after progression were treated with ibrutinib. Conclusion: Our findings suggest that ibrutinib can achieve relatively prolonged control of MCL progressing after autoSCT.