Disseminated fusariosis after allogenic hematopoietic stem cell transplantation: case report.

In allogenic stem cell recipients, invasive fungal disease is a common yet dreaded complication with high mortality. Among these, fusariosis is especially complex to treat due to high intrinsic resistance and few antimycotic options, requiring close cooperation of all involved departments. We here report an instructive case of disseminated fusariosis after allogenic stem cell transplantation with fatal outcome despite maximum treatment.

Prolonged Thrombocytopenia and Severe Transfusion Reaction after ABO-Incompatible Allogeneic Hematopoietic Stem Cell Transplantation in a Patient with Chronic Myelomonocytic Leukemia.

Introduction: Major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HCT) is a common practice and represents a challenging transfusion scenario. Prolonged thrombocytopenia with increased platelet transfusion needs is one of its reported adverse effects, and this has been linked to the persistence of recipient anti-donor isoagglutinins. Case Presentation: A 55-year-old male patient, O Rh(D)-positive, with chronic myelomonocytic leukemia underwent major incompatible allo-HCT from a A Rh(D)-negative donor. He presented with prolonged thrombocytopenia and multiple transfusion reactions after A Rh(D)-negative platelet transfusions. Considering the outcomes of numerous examinations, we tested the anti-A1 titers, finding a significant persistence of anti-donor isoagglutinins. We limited platelet transfusions to blood group O Rh(D)-negative donors, which significantly decreased the requirement for platelet transfusions. In addition, the transfusion reactions ceased. Conclusion: In case of transfusion reactions against platelet products in major ABO-incompatible allo-HCT patients, isoagglutinin monitoring should be considered and a change in the platelet transfusion protocol may be beneficial in patients presenting high isotiters against recipient's blood type.

Transplant-Associated Thrombotic Microangiopathy in the Context of Allogenic Hematopoietic Stem Cell Transplantation: Where We Stand.

Transplant-associated thrombotic microangiopathy (TA-TMA) constitutes a significant contributor to the increased morbidity and mortality after allogenic hematopoietic stem cell transplantation (allo-HSCT). TA-TMA is a heterogenous disease, characterized by the triad of endothelial cell activation, complement dysregulation and microvascular hemolytic anemia, which may affect all organs. The lack of consensus diagnostic criteria, along with the common clinical features mimicking other diseases that complicate allo-HSCT, make the diagnosis of TA-TMA particularly challenging. Significant effort has been made to recognize specific risk factors predisposing to the development of TA-TMA and to identify serum biomarkers predicting the development of the disease. With regard to treatment, therapeutic plasma exchange (TPE) has been traditionally used, although with doubtful efficacy. On the other hand, the pivotal role of complement activation in the pathophysiology of TA-TMA has led to the exploration of the therapeutic potential of complement inhibitors in this setting. Eculizumab has been proposed as a first-line therapeutic agent in TA-TMA, owing to the very promising results in both pediatric and adult clinical trials. Pharmacokinetic and pharmacodynamic studies and CH50 levels are of paramount importance in the allo-HSCT setting, as a different dosing schedule (more intensive-in dose and frequency-at the beginning) seems to be required for successful outcomes. Furthermore, Narsoplimab, a MASP-2 inhibitor, recently received a Breakthrough Therapy Designation from the FDA for the treatment of TA-TMA after allo-HSCT. Finally, the decision to withdraw the CNIs, although initially advised by the Bone and Marrow Transplant Clinical Trials Network Committee, remains debatable owing to the controversial results of recent clinical trials. This review summarizes the current updates on pathophysiology, diagnosis and therapeutic approaches and emphasizes future goals and perspectives.

Systematic Review and Meta-Analysis of Health-Related Quality of Life in Patients with ß-Thalassemia that Underwent Hematopoietic Stem Cell Transplantation.

Background: ß-Thalassemia major (ß-TM) represents one of the most important hemoglobinopathies worldwide. Remarkable improvements have been achieved in supportive therapy based on blood transfusions and iron chelation, and nowadays, this approach is capable of assuring a long life in these patients in industrialized countries. The only curative treatment is represented by hematopoietic stem cell transplantation (HSCT). However, this treatment may be burdened by deterioration in the Health-Related Quality of Life (HRQoL). This paper aimed to evaluate the role of HRQoL in transplanted ß-TM patients with a systematic review and meta-analysis. Methods: PubMed database, Web of Science, and Scopus were systematically searched for studies published between January 1st, 2000 to September 2020. The following terms were entered in the database queries: ß-thalassemia, HRQoL, and HSCT. The study was carried out according to the Preferred Reporting Items for Systematic and Meta-analyses (PRISMA) statement. Results: We identified a total of 33 potential studies. Among these, 10 were finally considered in the systematic review and 5 in the meta-analysis. Overall, good scores in the principal domains of HRQoL were reported by transplanted patients. These data were confirmed by results of meta-analysis that showed significant difference between transplanted and ß-TM patients treated with conventional therapy in the physical and emotional dimension, with a medium effect size [d=0.65, 95% CI (0.29-1.02), z = 3.52, p =0.0004, I2=75%; and d=0.59, 95% CI (0.43-0.76), z = 6.99, p <0.00001, I2=0%, respectively]. Conclusion: HRQoL is generally good in ß-TM transplanted patients and may significantly contribute in deciding whether or not to transplant a ß-TM patient treated with conventional therapy.

Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia.

BACKGROUND: The epigenetic regulator additional sex combs-like 1 (ASXL1) is an adverse prognostic factor in acute myeloid leukemia (AML). However, the mutational spectrum and prognostic factors of ASXL1-mutated (ASXL1+) AML are largely unknown. We aim to evaluate the risk factors influencing the prognosis of ASXL1+ AML. METHODS: We performed next-generation sequencing (NGS) in 1047 cases of de novo AML and discovered 91 ASXL1+ AML (8.7%). The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. RESULTS: In a total of 91 ASXL1+ AML, 86% had one or more co-mutations. The factors that had adverse impact on overall survival (OS) and event-free survival (EFS) are defined as high risk factors, including age ≥ 60 years, WBC count ≥ 50 × 109/L, FLT3-ITD mutations, RUNX1 mutations, and absence of AML1-ETO fusion gene. ASXL1 mutations without any risk factor were classified as single-hit ASXL1+ AML; ASXL1 mutations accompanied with one of the risk factors was referred to as double-hit ASXL1+ AML; ASXL1 mutations with two or more of the risk factors were designated as triple-hit ASXL1+ AML. The combination of these risk factors had a negative influence on the prognosis of ASXL1+ AML. The median OS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 6.67 months in triple-hit ASXL1+ AML (P = 0.003). The median EFS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 5.47 months in triple-hit ASXL1+ AML (P = 0.002). Allogenic hematopoietic stem cell transplantation (allo-HSCT) improved the prognosis of double/triple-hit ASXL1+ AML patients. CONCLUSIONS: Our study provided new insights into the mutational spectrum and prognostic factors of ASXL1+ AML patients. Our primary data suggest that the risk factors in ASXL1+ AML contribute to the poor outcome of these patients. The management of ASXL1+ AML patients should be based on the risk factors and allo-HSCT is highly recommended for consolidation.

Lung transplantation for late-onset non-infectious chronic pulmonary complications of allogenic hematopoietic stem cell transplant.

BACKGROUND: Late onset non-infectious pulmonary complications (LONIPCs) following allogenic hematopoietic stem cell transplantation (allo-HSCT) confer a significant mortality risk. Lung transplantation (LTx) has the potential to provide survival benefit but the impact of prior allo-HSCT on post-LTx outcomes is not well studied. METHODS: This retrospective, single-centre cohort study assessed the post-LTx outcomes of adults with LONIPCs of allo-HSCT. Outcomes of LTx for LONIPCs were compared to propensity-score matched LTx controls (n = 38, non-HSCT) and recipients of re-LTx (n = 70) for chronic lung allograft dysfunction (CLAD). RESULTS: Nineteen patients underwent DLTx for LONIPCs of allo-HSCT between 2003 and 2019. Post-LTx survival was 50% at 5-years. Survival to 1-year post-LTx was similar to matched controls (p = 0.473). Survival, conditional on 1-year survival, was lower in the allo-HSCT cohort (p = 0.034). An increased risk of death due to infection was identified in the allo-HSCT cohort compared to matched controls (p = 0.003). Compared to re-LTx recipients, the allo-HSCT cohort had superior survival to 1-year post-LTx (p = 0.034) but conditional 1-year survival was similar (p = 0.145). CONCLUSION: This study identifies an increased risk of post-LTx mortality in recipients with previous allo-HSCT, associated with infection. It supports the hypothesis that allo-HSCT LTx recipients are relatively more immunosuppressed than patients undergoing LTx for other indications. Optimisation of post-LTx immunosuppressive and antimicrobial strategies to account for this finding should be considered.

Prognosis and risk factors for central nervous system relapse after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia.

We performed a nested case-control study to investigate the incidence, treatment, and prognosis of central nervous system (CNS) relapse after allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) and compared the outcomes of patients with CNS relapse following haploidentical donor (HID) HSCT versus identical sibling donor (ISD) HSCT. A total of 37 patients (HID-HSCT, 24; ISD-HSCT, 13) developed CNS relapse after transplantation between January 2009 and January 2019, with an incidence of 1.81%. The median time from transplantation to CNS relapse was 239 days. Pre-HSCT CNS involvement (HR 6.940, 95% CI 3.146-15.306, p < .001) was an independent risk factor for CNS relapse after allo-HSCT for AML. The 3-year overall survival (OS) for patients with CNS relapse was 60.3 ± 8.8%, which was significantly lower than that in the controls (81.5 ± 4.5%, p = .003). The incidence of CNS relapse was 1.64% for patients who received HID-HSCT and 2.55% for those who received ISD-HSCT (p = .193). There was no significant difference in OS between the HID-HSCT and ISD-HSCT subgroups among the patients with CNS relapse. In conclusion, CNS relapse is a rare but serious complication after allo-HSCT for AML, and the incidence and outcomes of patients with CNS relapse are comparable following HID-HSCT and ISD-HSCT.

Single-center experience with use of letermovir for treatment of CMV infection in stem cell transplant recipients.

The approval of letermovir provided a new option for cytomegalovirus (CMV) prophylaxis in CMV seropositive allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Data are limited on the use of letermovir for the treatment of CMV infection. We performed a single-center retrospective review of allo-HSCT recipients who received letermovir off-label for treatment of CMV infection (CMV DNAemia and CMV disease) from November 2017 until November 2019. Fifteen patients were included, 14 of which received letermovir for treatment of CMV DNAemia. The median duration from transplant to CMV DNAemia was 41 days and median duration of letermovir therapy was 53 days (IQR, 43-59). Median time to first undetectable CMV viral load from the start of letermovir was 16 days (IQR, 13-21). No significant correlation was noted between the time to CMV DNA clearance and either CMV DNA at the time of starting letermovir (r = -.12, 95% CI: -0.63-0.46; P = .69) or CMV DNA peak (r = .04, 95% CI: -0.51-0.58, P = .87). Three patients had late reactivation of CMV after completion of letermovir (20%) after 87 days (IQR, 68-103) of therapy cessation. Clinical failure or treatment intolerance occurred in two patients (14%). One patient failed to achieve an undetectable viral load. In another patient, letermovir was discontinued due to documented therapy-related thrombocytopenia. Our analysis suggests that letermovir might have a potential role for the treatment of CMV infection in select patients with contraindication or intolerance to more validated therapies.

Impact of Donor Source on Allogeneic Hematopoietic Stem Cell Transplantation for Mature T Cell and Natural Killer Cell Neoplasms in the Kyoto Stem Cell Transplantation Group.

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the key strategy to cure patients with mature T and natural killer (NK) cell lymphomas/leukemia, especially those with relapsed/refractory diseases, there is no consensus strategy for donor selection. We retrospectively analyzed the outcomes of allo-HSCT in 111 patients in 15 Japanese institutions as a multi-institutional joint research project. Thirty-nine patients received bone marrow or peripheral blood stem cell transplantation from related donors (rBMT/rPBSCT), 37 received BMT/PBSCT from unrelated donors (uBMT/uPBSCT), and 35 received cord blood transplantation (CBT). Overall survival (OS) and progression-free survival (PFS) at 4 years were 42% and 34%, respectively. The cumulative incidences of relapse and nonrelapse mortality were 43% and 25%. In multivariate analysis, CBT showed comparable OS with rBMT/rPBSCT (rBMT/rPBSCT versus CBT: hazard ratio [HR], 1.63; P = .264) and better OS compared with uBMT/uPBSCT (HR, 2.99; P = .010), with a trend toward a lower relapse rate (rBMT/rPBSCT versus CBT: HR, 2.60; P = .010; uBMT/uPBSCT versus CBT: HR, 2.05; P = .082). This superiority of CBT was more definite in on-disease patients (OS: rBMT/rPBSCT versus CBT: HR, 5.52; P = .021; uBMT/uPBSCT versus CBT: HR, 6.80; P = .007). Better disease control was also strongly associated with better OS and PFS with lower relapse rate. In conclusion, allo-HSCT is beneficial for the survival of patients with mature T and NK cell lymphomas/leukemia if performed in a timely fashion. Since CBT showed favorable survival with a lower relapse risk, it could be a preferred alternative, especially in on-disease patients.

The role of allogeneic hematopoietic stem cell transplantation and Epstein-Barr virus infection on the treatment for child primary hemophagocytic lymphohistiocytosis patients with X-linked lymphoproliferative disease: A rare case report and family survey study.

XLP-2 is known as a rare primary immunodeficiency disease, which is characterized by the susceptibility to EBV infection and potential development into the pHLH. The existing studies believe that the dysfunction of XIAP represents one of the most significant pathogenic mechanisms of XLP-2, and allo-HSCT is regarded as a crucial treatment for the long-term survival in XLP-2 patients. In our present study, a 2-year-old male patient was diagnosed with XLP-2. After receiving chemotherapy by using HLH-2004 without allo-HSCT, he reached a complete remission, and his EBV load was brought under control. Our family survey revealed a novel frameshift mutation in the XIAP gene in this patient, as well as in his cousin and grandfather. Until now, the patient has been followed up for 22 months with no recurrence reported yet. Based on these findings, it is believed that for child pHLH patients with XLP-2, the treatment by controlling symptoms alone without allo-HSCT and with regular monitoring of EBV load could be conducive to a long-term survival.

Juvenile Blastic Plasmacytoid Dendritic Cell Neoplasm.

is missing (Short communication).

Low cyclosporine concentrations in children and time to acute graft versus host disease.

BACKGROUND: Achievement of target blood concentrations of cyclosporine (CsA) early after transplantation is known to be highly effective for reducing the incidence of acute graft versus host disease (aGVHD). However, no research has been conducted for predicting aGVHD occurrence with low CsA concentrations at different time periods. The objective of this study was to investigate the risk of aGVHD according to low CsA concentrations at lag days in children with allogenic hematopoietic stem cell transplantation (HSCT). METHODS: The records of 61 consecutive children who underwent allogeneic HSCT and received CsA as prophylaxis against aGVHD between May 2012 and March 2015 were retrospectively evaluated. The main outcome was any association between low CsA concentrations at lag days and aGVHD occurrence, which was examined for the first month after transplantation. Mean CsA concentrations at three lag periods were calculated: lag days 0-6, 7-13, and 14-20 before aGVHD occurrence. RESULTS: Patients whose mean CsA concentrations at lag days 0-6 did not reach the initial target concentration had 11.0-fold (95% confidence interval [CI]: 2.3-51.9) greater incidence of aGVHD. In addition, the AORs of low CsA concentrations at lag days 7-13 and 14-20 for developing aGVHD were 108.2 (95% CI: 7.7-1515.5) and 12.1 (95% CI: 1.1-138.1), respectively. CONCLUSIONS: After low CsA concentrations are detected, careful attention needs to be paid to prevent aGVHD.

Hematopoietic Stem Cell Transplantation for Mucopolysaccharidoses: Past, Present, and Future.

Allogenic hematopoietic stem cell transplantation (HSCT) has proven to be a viable treatment option for a selected group of patients with mucopolysaccharidoses (MPS), including those with MPS types I, II, IVA, VI, and VII. Early diagnosis and timely referral to an expert in MPS are critical, followed by a complete examination and evaluation by a multidisciplinary team, including a transplantation physician. Treatment recommendations for MPS are based on multiple biological, sociological, and financial factors, including type of MPS, clinical severity, prognosis, present clinical signs and symptoms (disease stage), age at onset, rate of progression, family factors and expectations, financial burden, feasibility, availability, risks and benefits of available therapies such as HSCT, enzyme replacement therapy (ERT), surgical interventions, and other supportive care. International collaboration and data review are critical to evaluating the therapeutic efficacy and adverse effects of HSCT for MPS. Collaborative efforts to assess HSCT for MPS have been ongoing since the first attempt at HSCT in a patient with MPS reported in 1981. The accumulation of data since then has made it possible to identify early outcomes (ie, transplantation outcomes) and long-term disease-specific outcomes resulting from HSCT. The recent identification of predictive factors and the development of innovative regimens have significantly improved the outcomes of both engraftment failure and transplantation-related mortality. Assessment of long-term outcomes has considered a variety of factors, including type of MPS, type of graft, age at transplantation, and stage of disease progression, among others. Studies on long-term outcomes are considered a key factor in the use of HSCT in patients with MPS. These studies have shown the effects and limitations of HSCT on improving disease manifestations and quality of life. In this review, we summarize the efficacy, side effects, risks, and cost of HSCT for each type of MPS.

Phase I/II Trial of a Combination of Anti-CD3/CD7 Immunotoxins for Steroid-Refractory Acute Graft-versus-Host Disease.

Effective therapies for treating patients with steroid-refractory acute graft-versus-host-disease (SR-aGVHD), particularly strategies that reduce the duration of immunosuppression following remission, are urgently needed. The investigated immunotoxin combination consists of a mixture of anti-CD3 and anti-CD7 antibodies separately conjugated to recombinant ricin A (CD3/CD7-IT), which induces in vivo depletion of T cells and natural killer (NK) cells and suppresses T cell receptor activation. We conducted a phase I/II trial to examine the safety and efficacy of CD3/CD7-IT in 20 patients with SR-aGVHD; 17 of these patients (85%) had severe SR-aGVHD, and all 20 patients had visceral organ involvement, including 18 (90%) with gastrointestinal (GI) involvement and 5 (25%) with liver involvement. A validated 2-biomarker algorithm classified the majority of patients (11 of 20) as high risk. On day 28 after the start of CD3/CD7-IT therapy, the overall response rate was 60% (12 of 20), with 10 patients (50%) achieving a complete response. The 6-month overall survival rate was 60% (12 of 20), including 64% (7 of 11) classified as high risk by biomarkers. The 1-week course of treatment with CD3/CD7-IT caused profound but transient depletion of T cells and NK cells, followed by rapid recovery of the immune system with a diverse TCR Vß repertoire, and preservation of Epstein-Barr virus- and cytomegalovirus-specific T cell clones. Furthermore, our results indicate that CD3/CD7-IT appeared to be safe and well tolerated, with a relatively low prevalence of manageable and reversible adverse events, primarily worsening of hypoalbuminemia, microangiopathy, and thrombocytopenia. These encouraging results suggest that CD3/CD7-IT may improve patient outcomes in patients with SR-aGVHD.

The benefit of chronic graft-versus-host disease in patients with acute myeloid leukemia relapsed after allogeneic stem cell transplantation.

To investigate the effect of chronic graft-versus-host disease (cGVHD) on the outcomes of acute myeloid leukemia (AML) patients who relapsed after allogenic hematopoietic cell transplantation, we performed a retrospective analysis on 218 patients with a median follow-up of 21.4 (3.4-179.6) months. A total of 103 patients developed cGVHD, with a 2-year cumulative incidence of 48.9% (95% CI 42.1-55.7%). The estimated 3-year overall survival was 85.7% (95% CI 75.7-95.7%), 48.8% (95% CI 31.7-66.0%), and 54.1% (95% CI 44.3-63.8%) for patients with limited cGVHD, extensive cGVHD, and without cGVHD (P < 0.001). The 3-year event-free survival were 75.5% (95% CI 63.7-87.4%), 46.0% (95% CI 28.8-63.2%), and 45.0% (95% CI 35.6-54.4%) (P < 0.001), while the 3-year cumulative relapse rates were 22.8% (95% CI 11.0-34.6%), 11.6% (95% CI 5.3-22.6%), and 40.3% (95% CI 31.0-49.6%), respectively (P < 0.001). At the last evaluation, 62 patients relapsed with 17 patients having active cGVHD and 45 without. Compared to patients relapsing without cGVHD, patients who relapsed with cGVHD had a longer duration of remission and a better 2-year post-relapse survival [10.9 months (3.7-42.2) versus 4.4 months (2.2-28.3); P < 0.001]; [32.8% (95% CI 8.2-57.4%) versus 4.5% (95% CI 0-12.8%); P = 0.043]. For patients who relapsed with cGVHD, the remission rates were both 60% after salvage chemotherapy with or without donor lymphocyte infusion (P = 1.000). In conclusion, cGVHD may exert a stronger graft-versus-leukemia effect, which may decrease the post-transplantation relapse rate and may also benefit those patients who eventually relapsed after transplantation in terms of prolong post-relapse survival.

Neutropenia and renal dysfunction due to intravesical cidofovir for virus-associated hemorrhagic cystitis after kidney and allogenic hematopoietic stem cell transplantations.

We present a patient with virus-associated hemorrhagic cystitis who underwent kidney and allogenic hematopoietic stem cell transplantations (allo-HSCT). Six months post-allo-HSCT, adenovirus hemorrhagic cystitis occurred, which has been in remission after a single dose of intravesical cidofovir. This might cause prolonged neutropenia and nephrotoxicity, suggesting cidofovir absorption in the blood.

Utility and Safety of Liver Biopsy in Patients with Undetermined Liver Blood Test Anomalies after Allogeneic Hematopoietic Stem Cell Transplantation: A Monocentric Retrospective Cohort Study.

Liver blood test anomalies are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but their cause often remains difficult to identify. Our objective was to evaluate the safety and utility of liver biopsies in patients who underwent allo-HSCT. In a retrospective single-center cohort study, we reviewed all cases of patients who underwent liver biopsy between June 2005 and July 2017. During this period, 54 biopsies were performed in 45 patients, in which 38 patients underwent allo-HSCT for malignant and 7 for nonmalignant hematological disorders. Median time between allo-HSCT and liver biopsy was 213 days. Seven biopsies were percutaneous, and 47 were transjugular. No adverse event related to the biopsy procedure occurred; 94.5% biopsies (51 of 54) led to a histological diagnosis. Cholestatic graft-versus-host disease was histologically demonstrated in 16 biopsies (30%); hepatitis-like graft-versus-host disease in 9 biopsies (17%); nonalcoholic steatohepatitis in 6 biopsies (9%); regenerative nodular hyperplasia in 4 biopsies (5%); and drug-induced liver injury, sinusoidal obstruction syndrome, and viral hepatitis each in 3 biopsies (5%). Association between clinical, laboratory, imaging and pathological features was poor. Only 34% of physicians' prebiopsy hypotheses were confirmed by pathological findings. Patient management was influenced by liver biopsy results in 65% of cases, allowing us to identify a new diagnosis (n = 13), rule out a differential diagnosis (n = 14), or confirm the main hypothesis (n = 6). In conclusion, liver biopsy is a safe and useful technique to investigate liver blood test anomalies following allo-HSCT.

Delayed platelet recovery after allogeneic hematopoietic stem cell transplantation: Association with chronic graft-versus-host disease and survival outcome.

Delayed platelet recovery (DPR) despite prompt neutrophil engraftment is frequently observed after allogeneic hematopoietic stem cell transplantation (HSCT). However, few studies have evaluated the risk factors and long-term outcome. Therefore, we retrospectively analysed 219 adult patients who underwent their first allogenic HSCT with neutrophil engraftment. Of these 219 patients, 50 (22.8%) had DPR that was defined as relapse-free survival at day 60 after HSCT without primary platelet recovery despite neutrophil engraftment. The results of a multivariate analysis showed that a high-risk underlying disease (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.04-5.48; P = .041) and human leukocyte antigen-mismatched HSCT (OR, 2.63; 95% CI, 1.28-5.43; P = .009) were associated with an increased risk of DPR. In univariate analyses, the occurrence of DPR was significantly associated with inferior overall survival, high nonrelapse mortality, and a low incidence of chronic graft-versus-host disease (GVHD), despite a comparable relapse rate. In multivariate analyses, DPR was associated with inferior overall survival (hazard ratio [HR], 2.00; 95% CI, 1.23-3.27; P = .005) and a low incidence of chronic GVHD (HR, 0.42; 95% CI, 0.22-0.78; P = .002). In conclusion, DPR was a strong predictor of shorter survival but also less frequent chronic GVHD.

Cardiac output response to exercise in patients before allogenic hematopoietic stem cell transplantation.

INTRODUCTION: High-dose chemotherapy for remission induction can induce cardiac toxicity prior to hematopoietic stem cell transplantation (HSCT). However, the details of cardiac function in patients undergoing HSCT are unclear, particularly during exercise. The aim of present study was to evaluate cardiac output responses to exercise in patients after high-dose chemotherapy before HSCT compared with in age-matched healthy controls. METHODS: Twenty-nine patients before HSCT (age 44.6 ± 15.2 years) and 13 controls (45.8 ± 16.0 years) performed the 6-min walk test (6MWT). Cardiac output (CO), stroke volume (SV), heart rate (HR), and cardiac index (CI) were continuously measured during the 6MWT using the noninvasive thoracic impedance method. RESULTS: No significant difference was observed in the six-minute walk distance (6MD) between the two groups. SV, CO, and CI both at rest and the end of the 6MWT in the patients were significantly lower, compared with the controls, but there was no significant difference in HR. In all subjects, the 6MD was positively correlated with SV, CO, CI, and HR after the 6MWT. CONCLUSION: These findings suggest that cardiac output response to exercise indicates exercise intolerance, which may not be detected by 6MD in patients before HSCT.

ITA-MNGIE: an Italian regional and national survey for mitochondrial neuro-gastro-intestinal encephalomyopathy.

Mitochondrial neuro-gastro-intestinal encephalomyopathy (MNGIE) is a rare and unavoidably fatal disease due to mutations in thymidine phosphorylase (TP). Clinically it is characterized by gastrointestinal dysfunction, malnutrition/cachexia and neurological manifestations. MNGIE diagnosis remains a challenge mainly because of the complexity and rarity of the disease. Thus, our purposes were to promote a better knowledge of the disease in Emilia-Romagna region (ERR) by creating an accurate and dedicated network; to establish the minimal prevalence of MNGIE in Italy starting from ERR. Blood TP activity level was used as screening test to direct candidates to complete diagnostic work-up. During the study period of 1 year, only 10/71 units of ERR recruited 14 candidates. Their screening did not show TP activity changes. An Italian patient not resident in ERR was actually proved to have MNGIE. At the end of study in Italy there were nine cases of MNGIE; thus, the Italian prevalence of the disease is ~0.15/1,000,000 as a gross estimation. Our study confirms that MNGIE diagnosis is a difficult process which reflects the rarity of the disease and, as a result, a low level of awareness among specialists and physicians. Having available novel therapeutic options (e.g., allogenic hematopoietic stem cell transplantation and, more recently, liver transplantation) and an easy screening test, an early diagnosis should be sought before tissue damage occurs irreversibly.