Stem cell therapy for dilated cardiomyopathy.

BACKGROUND: Stem cell therapy (SCT) has been proposed as an alternative treatment for dilated cardiomyopathy (DCM), nonetheless its effectiveness remains debatable. OBJECTIVES: To assess the effectiveness and safety of SCT in adults with non-ischaemic DCM. SEARCH METHODS: We searched CENTRAL in the Cochrane Library, MEDLINE, and Embase for relevant trials in November 2020. We also searched two clinical trials registers in May 2020. SELECTION CRITERIA: Eligible studies were randomized controlled trials (RCT) comparing stem/progenitor cells with no cells in adults with non-ischaemic DCM. We included co-interventions such as the administration of stem cell mobilizing agents. Studies were classified and analysed into three categories according to the comparison intervention, which consisted of no intervention/placebo, cell mobilization with cytokines, or a different mode of SCT. The first two comparisons (no cells in the control group) served to assess the efficacy of SCT while the third (different mode of SCT) served to complement the review with information about safety and other information of potential utility for a better understanding of the effects of SCT. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all references for eligibility, assessed trial quality, and extracted data. We undertook a quantitative evaluation of data using random-effects meta-analyses. We evaluated heterogeneity using the I² statistic. We could not explore potential effect modifiers through subgroup analyses as they were deemed uninformative due to the scarce number of trials available. We assessed the certainty of the evidence using the GRADE approach. We created summary of findings tables using GRADEpro GDT. We focused our summary of findings on all-cause mortality, safety, health-related quality of life (HRQoL), performance status, and major adverse cardiovascular events. MAIN RESULTS: We included 13 RCTs involving 762 participants (452 cell therapy and 310 controls). Only one study was at low risk of bias in all domains. There were many shortcomings in the publications that did not allow a precise assessment of the risk of bias in many domains. Due to the nature of the intervention, the main source of potential bias was lack of blinding of participants (performance bias). Frequently, the format of the continuous data available was not ideal for use in the meta-analysis and forced us to seek strategies for transforming data in a usable format. We are uncertain whether SCT reduces all-cause mortality in people with DCM compared to no intervention/placebo (mean follow-up 12 months) (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.54 to 1.31; I² = 0%; studies = 7, participants = 361; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection in people with DCM (data could not be pooled; studies = 7; participants = 361; very low-certainty evidence). We are uncertain whether SCT improves HRQoL (standardized mean difference (SMD) 0.62, 95% CI 0.01 to 1.23; I² = 72%; studies = 5, participants = 272; very low-certainty evidence) and functional capacity (6-minute walk test) (mean difference (MD) 70.12 m, 95% CI -5.28 to 145.51; I² = 87%; studies = 5, participants = 230; very low-certainty evidence). SCT may result in a slight functional class (New York Heart Association) improvement (data could not be pooled; studies = 6, participants = 398; low-certainty evidence). None of the included studies reported major adverse cardiovascular events as defined in our protocol. SCT may not increase the risk of ventricular arrhythmia (data could not be pooled; studies = 8, participants = 504; low-certainty evidence). When comparing SCT to cell mobilization with granulocyte-colony stimulating factor (G-CSF), we are uncertain whether SCT reduces all-cause mortality (RR 0.46, 95% CI 0.16 to 1.31; I² = 39%; studies = 3, participants = 195; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection (studies = 1, participants = 60; very low-certainty evidence). SCT may not improve HRQoL (MD 4.61 points, 95% CI -5.62 to 14.83; studies = 1, participants = 22; low-certainty evidence). SCT may improve functional capacity (6-minute walk test) (MD 140.14 m, 95% CI 119.51 to 160.77; I² = 0%; studies = 2, participants = 155; low-certainty evidence). None of the included studies reported MACE as defined in our protocol or ventricular arrhythmia. The most commonly reported outcomes across studies were based on physiological measures of cardiac function where there were some beneficial effects suggesting potential benefits of SCT in people with non-ischaemic DCM. However, it is unclear if this intermediate effects translates into clinical benefits for these patients. With regard to specific aspects related to the modality of cell therapy and its delivery, uncertainties remain as subgroup analyses could not be performed as planned, making it necessary to wait for the publication of several studies that are currently in progress before any firm conclusion can be reached. AUTHORS' CONCLUSIONS: We are uncertain whether SCT in people with DCM reduces the risk of all-cause mortality and procedural complications, improves HRQoL, and performance status (exercise capacity). SCT may improve functional class (NYHA), compared to usual care (no cells). Similarly, when compared to G-CSF, we are also uncertain whether SCT in people with DCM reduces the risk of all-cause mortality although some studies within this comparison observed a favourable effect that should be interpreted with caution. SCT may not improve HRQoL but may improve to some extent performance status (exercise capacity). Very low-quality evidence reflects uncertainty regarding procedural complications. These suggested beneficial effects of SCT, although uncertain due to the very low certainty of the evidence, are accompanied by favourable effects on some physiological measures of cardiac function. Presently, the most effective mode of administration of SCT and the population that could benefit the most is unclear. Therefore, it seems reasonable that use of SCT in people with DCM is limited to clinical research settings. Results of ongoing studies are likely to modify these conclusions.

Terminal ileum is the most sensitive site for the histologic diagnosis of grade 4 graft-versus-host disease (GvHD) in the lower GI tract and is a harbinger of poor outcome.

The site of the gastrointestinal (GI) tract where biopsies are most likely to be diagnostic of graft-versus-host disease (GvHD) remains controversial. Recent reports have indicated that biopsies from the rectosigmoid have sufficient sensitivity and specificity for diagnosing GI GvHD and can be obtained via a less invasive flexible sigmoidoscopy procedure. While GvHD histologic grades 1-3 have little correlation with patients' symptoms and overall clinical grade, histologic grade 4 GvHD does correlate with severe clinical presentation and a poor prognosis. We examined cases of lower GI biopsies obtained via a complete colonoscopy with ileal intubation for the evaluation of GvHD within a 2-year period from patients who underwent stem cell transplantation. In our study cohort, grade 4 GvHD was significantly more likely to be identified in a terminal ileum biopsy than in a biopsy from another site in the lower GI tract. Significantly, 5 of 6 patients with histologic grade 4 GvHD diagnosed on ileal biopsies died from complication of severe GI GvHD. Given the poor prognosis of histologic grade 4 GvHD in the terminal ileum, the detection of this finding may serve to inform clinicians that escalation or modification of treatment may need to be considered. Furthermore, our findings suggest that terminal ileal biopsies may help to increase sensitivity for identifying patients at high risk for poor outcome of GvHD.

Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia.

PURPOSE: Reduced-intensity conditioning (RIC) regimens have extended the curative potential of allogeneic stem-cell transplantation to older adults with high-risk acute myeloid leukemia (AML) and myelodysplasia (MDS) but are associated with a high risk of disease relapse. Strategies to reduce recurrence are urgently required. Registry data have demonstrated improved outcomes using a sequential transplant regimen, fludarabine/amsacrine/cytarabine-busulphan (FLAMSA-Bu), but the impact of this intensified conditioning regimen has not been studied in randomized trials. PATIENTS AND METHODS: Two hundred forty-four patients (median age, 59 years) with high-risk AML (n = 164) or MDS (n = 80) were randomly assigned 1:1 to a fludarabine-based RIC regimen or FLAMSA-Bu. Pretransplant measurable residual disease (MRD) was monitored by flow cytometry (MFC-MRD) and correlated with outcome. RESULTS: There was no difference in 2-year overall survival (hazard ratio 1.05 [85% CI, 0.80 to 1.38] P = .81) or cumulative incidence of relapse (CIR) (hazard ratio 0.94 [95%CI, 0.60 to 1.46] P = .81) between the control and FLAMSA-Bu arms. Detectable pretransplant MFC-MRD was associated with an increased CIR (2-year CIR 41.0% v 20.0%, P = .01) in the overall trial cohort with a comparable prognostic impact when measured by an unsupervised analysis approach. There was no evidence of interaction between MRD status and conditioning regimen intensity for relapse or survival. Acquisition of full donor T-cell chimerism at 3 months abrogated the adverse impact of pretransplant MRD on CIR and overall survival. CONCLUSION: The intensified RIC conditioning regimen, FLAMSA-Bu, did not improve outcomes in adults transplanted for high-risk AML or MDS regardless of pretransplant MRD status. Our data instead support the exploration of interventions with the ability to accelerate acquisition of full donor T-cell chimerism as a tractable strategy to improve outcomes in patients allografted for AML.

Allogeneic stem cell transplant in patients with acute myeloid leukemia and karnofsky performance status score less than or equal to 80%: A study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT).

Limited data are currently available on the outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (allo-SCT) with a reduced performance status. We herein present the results of a registry study on 2,936 AML patients undergoing allo-SCT in first remission (CR1) with a Karnofsky Performance Status (KPS) score less than or equal to 80%. Two-year leukemia-free survival (LFS), overall survival (OS) and graft-versus-host disease (GVHD)-free, and relapse-free survival (GRFS) rates were 54%, 59%, and 41%, respectively. In multivariable analysis, patients with a KPS score = 80% had lower non-relapse mortality (NRM) and superior OS in comparison to patients with a KPS score <80% (p < 0.001). In the subgroup of patients with a KPS score =80%, a reduced-intensity conditioning (RIC) regimen was associated with an increased risk of relapse (p = 0.002) and lower GRFS (p < 0.001) compared to myeloablative conditioning (MAC). Differently, in patients with a KPS score <80%, a RIC regimen resulted in lower NRM (p < 0.001), whereas relapse incidence did not differ, thus leading to an improved GRFS (p = 0.008) as compared to MAC. A transplant from a matched sibling donor (MSD) was associated with a reduced incidence of grade III-IV acute GVHD (p < 0.01) and NRM (p < 0.01) in comparison to other donor types. In conclusion, allo-SCT appears feasible in AML patients with a jeopardized KPS score. Survival is significantly affected by the conditioning intensity, which should be adjusted according to the severity of KPS impairment.

Post-transplant consolidation based on combination of lenalidomide and proteasome inhibitors in multiple myeloma.

Multiple myeloma (MM) is a hematological malignancy due to uncontrolled proliferation of neoplastic plasma cells in the bone marrow, associated to chromosomal instability and cytogenetic abnormalities, which could have an impact on prognosis. Response to treatment and survival of newly diagnosed myeloma patients is heterogeneous, with median overall survival ranging from two to more than ten years, due to clinical and biological factors. To warrant long-term control of disease, several strategies have been proposed in the last years, including short-term high-dose of treatment, named as consolidation, before maintenance. This review will discuss the role of consolidation in the current myeloma treatment landscape, and further improvements required to optimize tailored front-line therapy.

Comparable Outcomes Between Unrelated and Haploidentical Stem Cell Transplantation in Adult Patients With Severe Aplastic Anemia.

BACKGROUND: Regarding patients with severe aplastic anemia (SAA) who fail immunosuppressive therapy and lack an HLA-matched sibling donor (MSD), the best alternative donor including unrelated (URD) and haploidentical (HAPLO) donors for allogeneic stem cell transplantation (SCT) remains to be established. METHODS: We analyzed the comprehensive outcomes of 153 consecutive adult SAA patients treated with SCT from alternative donors: 73 HLA-well matched (8/8) URDs (WM-URDs), 34 mismatched (6-7/8) URDs (MM-URDs), and 46 HAPLOs. RESULTS: Neutrophil/platelet engraftments were achieved at a median of 11/15 days for WM-URDs, 13/16.5 days for MM-URDs, and 12/14 days for HAPLOs, respectively. The 3-year overall survival (OS), failure-free survival, cumulative incidence of graft-failure, and transplant-related mortality were statistically not different among the 3 groups: 90.3%, 87.5%, 2.7%, and 9.8% for WM-URDs; 85.3%, 81.7%, 0%, and 14.7% for MM-URDs, and 84.4%, 82.3%, 6.5%, and 11.2% for HAPLOs, respectively. The rates of other complications, including graft-versus-host disease, cytomegalovirus DNAemia, hemorrhagic cystitis, invasive fungal disease, secondary malignancies, and sinusoidal obstruction syndrome, were also statistically not different. Subgroup analysis of the MM-URD group showed that the 3-year OS of patients receiving SCTs from 6/8-URDs were worse than those receiving SCTs from 7/8-URDs (75.0% versus 94.4%, P = 0.26). CONCLUSIONS: There was no significant difference in the SCT outcomes with WM-URDs, MM-URDs, or HAPLO donors. The clinician can make the best choice among these alternative donor sources based on the host/donor features and the urgency of the need for SCT. However, the selection of 6/8-URDs should be avoided due to inferior survival outcomes.

Attempts to optimize postinduction treatment in childhood acute myeloid leukemia without core-binding factors: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG).

We previously reported that risk-stratified therapy and intensive postremission chemotherapy (PRC) contributed to the improved survival of childhood acute myeloid leukemia (AML) in the AML99 study, which led us to consider a reduction in the number of PRC courses with more restrictive indications for stem cell transplantation (SCT) in the successor AML-05 study. We here report the outcome of AML patients without core-binding factor mutation (non-CBF AML) in the AML-05 study. Two-hundred eighty-nine children (age < 18 years old) with non-CBF AML were eligible. Patients with unfavorable cytogenetics and/or poor bone marrow response to the first induction course were candidates for SCT in the AML-05 study. After two courses of induction, a further three courses of PRC were given in AML-05, while four courses were given in the AML99 study. The 3-year event-free survival (EFS) rate in the AML-05 study (46.7%, 95% CI: 40.6-52.6%) was comparable to that of non-CBF AML in the AML99 study (51.5%, 95% CI: 42.7-59.6%) (P = .16). However, the 3-year overall survival (OS) rate in the AML-05 study (62.9%, 95% CI: 56.3-68.8%) was slightly lower than that in the AML99 study (71.6%, 95% CI: 63.2-78.5%) (P = .060), mainly due to decreased remission induction rate and increased nonrelapsed mortality. In conclusion, reductions in the number of PRC courses from four to three, together with repetitive cycles of high-dose cytarabine, were acceptable for non-CBF childhood AML.

Nutritional status as a predictor of adverse events and survival in pediatric autologous stem cell transplant.

Nutritional status is recognized as an independent and modifiable risk factor of outcome in stem cell transplant. Our research aim was to evaluate the impact of body mass index (BMI) and serum albumin on the prevalence of adverse events and survival in autologous transplant in children. A retrospective study was conducted of autologous transplants performed between 2006 and 2017 in the Children's Hospital Zagreb, Croatia. Nutritional status was assessed at the times of diagnosis, procedure, and discharge using BMI (underweight, normal, obese) and serum albumin (grades 1-4). Adverse events (fever, gastrointestinal toxicity, electrolyte disturbances, dysglycemia) and outcome (3-year, relapse, mortality) were documented. Seventy-seven children (54.5% males, mean age 7.9 years) underwent autologous transplant, mostly for neuroblastoma. In terms of BMI and albumin, which showed significant positive correlation at diagnosis (p = 0.026) and transplant (p = 0.016), most participants were well nourished. Average post-transplant weight loss was 4%. Major toxicities were severe mucositis (72.7%) and hypophosphatemia (31.2%). Relapse and mortality rates were 35.1% and 42.9%, respectively. Hypokalemia (p = 0.041) and hypomagnesemia (p = 0.044) were more prevalent in the underweight group, while obese children experienced significantly less severe mucositis (p = 0.016) and hypophosphatemia (p = 0.038). There was no significant difference regarding outcome among children of different nutritional status, although undernourished children tended to have lower relapse and mortality rates. In conclusion, underweight children are significantly more prone to severe electrolyte disorders and mucositis, and although statistical significance was not reached, are more likely to survive.

PD-L1 expression in bone marrow plasma cells as a biomarker to predict multiple myeloma prognosis: developing a nomogram-based prognostic model.

PD-L1 expression is associated with poor prognosis, although this relationship is unclear in bone marrow-derived haematologic malignancies, including multiple myeloma. We aimed to determine whether PD-L1 expression could predict the prognosis of newly diagnosed multiple myeloma (NDMM). We evaluated 126 NDMM patients (83, retrospectively; 43, prospectively) who underwent bone marrow examinations. Bone marrow aspirates were analysed for PD-L1 expression, categorized as low or high expression, using quantitative immunofluorescence. High PD-L1 expression could independently predict poor overall survival (OS) (95% CI = 1.692-8.346) in multivariate analysis. On subgroup analysis, high PD-L1 expression was associated with poor OS (95% CI = 2.283-8.761) and progression-free survival (95% CI = 1.024-3.484) in patients who did not undergo autologous stem cell transplantation (ASCT) compared with those who did. High PD-L1 expression was associated with poor OS despite frontline treatments with or without immunomodulators. Thus, PD-L1 expression can be a useful prognosis predictor in NDMM patients, whereas ASCT may be used in patients with high PD-L1 expression. We developed a prognostic nomogram and found that a combination of PD-L1 expression in bone marrow plasma cells and clinical parameters (age, cytogenetics, and lactate dehydrogenase) effectively predicted NDMM prognosis. We believe that our nomogram can help identify high-risk patients and select appropriate treatments.

Clinicopathologic predictors of renal outcomes in light chain cast nephropathy: a multicenter retrospective study.

Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. Severe renal impairment influences the allocation of chemotherapy and its tolerability; it also affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, and renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with a mean estimated glomerular filtration rate (eGFR) of 13 ± 11 mL/min/1.73 m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 in the cortex. Tubulointerstitial lesions were frequent: acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), and cortical and medullary inflammation (95% and 75%, respectively). Medullary inflammation, giant cell reaction, and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43 ± 30 mL/min/1.73 m2. Age, ß2-microglobulin, best hematologic response, number of cortical casts per square millimeter, and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response, which, in turn, is associated with overall survival.

CXCL9 Predicts Severity at the Onset of Chronic Graft-versus-host Disease.

BACKGROUND: Chronic graft-versus-host disease (cGVHD) represents a double-edged sword. In its nonsevere form, cGVHD associates with better control of the malignant disease, thus highlighting graft-versus-leukemia effects. However, severe cGVHD leads to debilitating morbidity and increased nonrelapse mortality. The prediction of severe cGVHD, in particular at disease onset, is therefore of high importance for ensuing clinical decisions and overall success of allogeneic stem cell transplantations. CXC-chemokine ligand 9 (CXCL9) is an interferon-inducible chemokine of the CXC family and is increased in cGVHD. Endothelial activation and stress index (EASIX) was shown to predict death after acute graft-versus-host disease. We explored CXCL9 and EASIX as predictors of severe cGVHD. METHODS: Sera and clinical data of 480 patients were available who survived at least 6 months following allogeneic stem cell transplantation without steroid-refractory acute graft-versus-host disease and without early relapse. CXCL9 and EASIX were measured on day +100 and onset of cGVHD. RESULTS: Development of nonsevere cGVHD was significantly associated with improved overall survival (hazard ratio 0.53, P < 0.001). CXCL9 serum levels at the onset of cGVHD predicted the development of severe cGVHD later on (hazard ratio 1.33, P = 0.02). In contrast, EASIX at the onset of cGVHD was not associated with cGVHD severity but was a significant independent risk factor for overall mortality and nonrelapse mortality. CONCLUSIONS: CXCL9 levels at the onset of cGVHD can help to predict severe courses of the disease and have potential for optimizing tailored administration of immunosuppressive therapy.

IgM AL amyloidosis: delineating disease biology and outcomes with clinical, genomic and bone marrow morphological features.

This study evaluates newly diagnosed IgM (6%, n = 75/1174) vs. non-IgM light chain amyloidosis patients. IgM amyloid patients had lower light chains (12.5 vs. 22.5 mg/dL; p < 0.001). Heart (56% vs. 73%, p = 0.002) and >1 organ involvement (31% vs. 44%, p = 0.02) was less common in IgM amyloidosis, while soft tissue and peripheral nerve involvement was more common. t(11;14) was less common (27% vs. 50%, p = 0.008) in IgM amyloidosis. Rates of MYD88L265P and CXCR4WHIM mutation in IgM amyloidosis were 58% (29/50) and 17% (8/46). Diagnosis after hematopathology review in IgM amyloidosis was pure plasma cell neoplasm (PPCN) in 23% (16/70), lymphoplasmacytic neoplasm (LPL) in 63% (44/70) patients, and other (14%). LPL vs. PPCN groups had distinct genetic abnormalities: t(11;14): 0% (0/18) vs. 60% (9/15), p < 0.001; MYD88L265P mutation: 84% (27/32) vs. 0% (0/14), p < 0.001; CXCR4 mutation: 29% (8/28) vs. 0% (0/14), p = 0.04. Overall survival was shorter in IgM AL when stratified by Mayo 2012 stage; stage 1/2 (59 vs. 125.9 months, p = 0.003) and stage 3/4 (6.5 vs. 12.9 months, p = 0.075), likely due to lower hematologic response rates (6 months: 39% vs. 59%, p = 0.008). We characterized two subtypes of IgM amyloidosis (LPL/PPCN). This can aid in therapeutic decision-making, with treatment directed at the clonal disease.

A meta-analysis of arrhythmia endpoints in randomized controlled trials of transendocardial stem cell injections for chronic ischemic heart disease.

INTRODUCTION: The electrophysiologic impact of cell-based therapy on the injured myocardium remains highly controversial. We aimed to perform a meta-analysis of studies comparing arrhythmia burden following transendocardial stem cell therapy vs placebo in patients with chronic ischemic heart disease (CIHD). METHODS AND RESULTS: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched. No restriction of stem cell type was specified. The outcomes included sustained supraventricular or ventricular arrhythmias (VAs), sudden cardiac death (SCD), and resuscitated sudden cardiac arrest (SCA). Effect sizes were reported as odds ratio (OR) and 95% CI. Poisson regression was used to account for zero-events data. Twelve randomized trials that included 736 patients (384 in the cell therapy group and 352 in the placebo group) were analyzed. Six different cell types were used. Follow-up ranged from 6 to 12 months. There was a significant decrease in risk of SCD in the cell therapy group, (FE OR, 0.19 [0.04, 0.93]; P = .04). In subgroup analysis, there was a significantly lower risk of SCD or resuscitated SCA in the cell therapy group limited to studies that did not use skeletal myoblasts, (FE OR, 0.23 [0.06, 0.83]; P = .03). There was no significant difference in the incidence of sustained VA between groups (FE OR, 0.91 [0.47, 1.77]; P = .8), even after stratifying by cell type. There was no difference in supraventricular arrhythmias between groups. CONCLUSION: Nonskeletal myoblast transendocardial cell therapy was associated with a significantly lower risk of SCD or resuscitated SCA compared to control, with no proarrhythmic effects.

Tandem high-dose chemotherapy with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin regimens for pediatric high-risk brain tumors.

BACKGROUND: High-dose chemotherapy (HDC) and autologous stem-cell transplantation (auto-SCT) are used to improve the survival of children with high-risk brain tumors who have a poor outcome with the standard treatment. This study aims to evaluate the outcome of HDC/auto-SCT with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin (TTC/MEC) regimens in pediatric brain tumors. METHODS: We retrospectively analyzed the data of 33 children (median age 6 years) who underwent HDC/auto-SCT (18 tandem and 15 single) with uniform conditioning regimens. RESULTS: Eleven patients aged < 3 years at diagnosis were eligible for HDC/auto-SCT to avoid or defer radiotherapy. In addition, nine patients with high-risk medulloblastoma (presence of metastasis and/or postoperative residual tumor ≥ 1.5 cm2), eight with other high-risk brain tumor (six CNS primitive neuroectodermal tumor, one CNS atypical teratoid/rhabdoid tumor, and one pineoblastoma), and five with relapsed brain tumors were enrolled. There were three toxic deaths, and two of which were due to pulmonary complications. The main reason for not performing tandem auto-SCT was due to toxicities and patient refusal. The event-free survival (EFS) and overall survival (OS) rates of all patients were 59.4% and 80.0% at a median follow-up with 49.1 months from the first HDC/auto-SCT, respectively. The EFS/OS rates of patients aged < 3 years at diagnosis, high-risk medulloblastoma, other high-risk brain tumor, and relapsed tumors were 50.0/81.8%, 87.5/85.7%, 66.7/88.9%, and 20.0/60.0%, respectively. CONCLUSIONS: Although tandem HDC/auto-SCT with TTC/MEC regimens showed promising survival rates, treatment modifications are warranted to reduce toxicities. The survival rates with relapsed brain tumors were unsatisfactory despite HDC/auto-SCT, and further study is needed.

Clinical features and survival of patients with T-cell/histiocyte-rich large B-cell lymphoma: analysis of the National Cancer Data Base.

Using data from the National Cancer Data Base, 2010-2015, we examined characteristics and outcomes of T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL, N = 622) relative to unspecified diffuse large B-cell lymphoma (DLBCL-NOS, N = 91,588) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL, N = 2240). Socio-demographic characteristics of patients with THRLBCL resembled more NLPHL than DLBCL-NOS. Five-year overall survival in THRLBCL was 66% (95% confidence interval [CI], 60-71%). Adjusting for clinical and socio-economic covariates, THRLBCL was associated with better survival than DLBCL-NOS (adjusted hazard ratio, 0.80; 95%CI, 0.67-0.94). This association was similar in academic and community hospitals and consistent in a model stratified by the revised International Prognostic Index. Prognostic factors in THRLBCL included age, comorbidity index, and extranodal primary site, but not stage. Adjusted odds of prior NLPHL were 18.2 higher for THRLBCL (95%CI, 7.2-45.7) than DLBCL-NOS. These large-scale epidemiologic data support the relationship between THRLBCL and NLPHL, and suggest improved prognosis with modern rituximab-based immunochemotherapy.

Delayed autologous stem cell transplantation following cardiac transplantation experience in patients with cardiac amyloidosis.

This study sought to retrospectively investigate the outcomes of patients with light-chain amyloidosis (AL) with advanced cardiac involvement who were treated with a strategy of heart transplantation (HT) followed by delayed autologous stem cell transplantation (ASCT) at 1-year posttransplant. Patients with AL amyloidosis with substantial cardiac involvement have traditionally had very poor survival (eg, several months). A few select centers have reported their outcomes for HT followed by a strategy of early ASCT (ie, 6 months) for CA. The outcomes of patients undergoing a delayed strategy have not been reported. All patients with AL amyloidosis at a single institution undergoing evaluation for HT from 2004-2018 were included. Retrospective analyses were performed. Sixteen patients underwent HT (including two combined heart-kidney transplant) for AL amyloidosis. ASCT was performed in a total of nine patients to date at a median 13.5 months (12.8-32.9 months) post-HT. Survival was 87.5% at 1 year and 76.6% at 5 years, comparable to institutional outcomes for nonamyloid HT recipients. In addition to these 16 patients, two patients underwent combined heart-lung transplantation. A strategy of delayed ASCT 1-year post-HT for patients with AL amyloidosis is feasible, safe, and associated with comparable outcomes to those undergoing an earlier ASCT strategy.

Superior Survival in African American Patients Who Underwent Autologous Stem Cell Transplantation for Multiple Myeloma.

INTRODUCTION/BACKGROUND: African American (AA) individuals have a twofold higher incidence of multiple myeloma (MM) compared with other racial groups. Outcomes are affected by factors such as disparate access to care as well as differences in disease biology. PATIENTS AND METHODS: We conducted a single-institution analysis to evaluate the effect of AA race on outcomes of MM patients who underwent autologous stem cell transplantation (ASCT) in the pre-novel and novel agent era. RESULTS: Sixty-one (47%) patients were AA and 69 (53%) were non-AA. Overall, 78 (60%) patients received any novel agent before transplantation and 52 (40%) received only chemotherapy. More non-AA patients received initial induction with a proteasome inhibitor (40 [60%] vs. 17 [28%]; P = .0007), and were treated with post-ASCT maintenance therapy (28 [41%] vs. 14 [23%]; P = .04). Time from diagnosis to ASCT in AA patients was 10 (range, 4-144) versus 8 (range, 3-54) months in non-AA patients (P = .01). Despite this, treatment-free survival (TFS) was equivalent between the 2 groups (x vs. y). Furthermore, AA patients had greater median overall survival (OS) compared with non-AA patients (not reached vs. 108 months; P = .03) and significantly improved OS in multivariable Cox proportional hazards models (adjusted hazard ratio, 0.30; 95% confidence interval, 0.11-0.81; P = .017). Median OS, landmarked at the time of relapse, was improved in AA patients (not reached vs. 68 months for P = .05). CONCLUSION: Our study showed with long follow-up, equivalent TFS after ASCT in AA and non-AA patients yet improved OS. Post relapse survival is improved in AA patients suggesting a better response to salvage therapy.

Diagnostic and Clinical Impact of Staging 18F-FDG PET/CT in Mantle-Cell Lymphoma: A Two-Center Experience.

INTRODUCTION: The diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in staging mantle-cell lymphoma has not yet investigated. The aim of this 2-center retrospective study was to investigate the utility of 18F-FDG PET/CT in assessing nodal, splenic, bone marrow (BM), and gastrointestinal (GI) disease compared to CT, BM, and GI endoscopy; and to assess its clinical impact. PATIENTS AND METHODS: One hundred twenty-two patients with histologically proven mantle-cell lymphoma were included. PET/CT BM findings were considered positive if isolated/multiple focal uptake in the BM not explained by benign findings and/or diffuse BM uptake higher than liver with/without focal uptakes were present. PET/CT findings were considered positive for GI involvement in the presence of isolated/multiple focal uptake in the GI organ. RESULTS: All patients had positive PET/CT showing the presence of at least one hypermetabolic lesion, with the exception of one case. PET/CT results, compared to CT, detected more nodal and/or splenic lesions in 26 patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT for BM were 52%, 98%, 97%, 65%, and 74%; for GI 64%, 91%, 69%, 90%, and 85%; and for GI excluding diabetic patients, 78%, 92%, 72%, 94%, and 89%. PET/CT permitted upstaging of 21 cases and downstaging of 2. CONCLUSION: 18F-FDG PET/CT showed excellent detection rate in nodal and splenic disease-a rate better than CT. For BM and GI evaluation, in order to reach good accuracy, the selection of patients and the use of specific criteria for evaluation of these organs seems to be crucial. Moreover, PET/CT altered the management and therapeutic approach in about 20% of patients.