The Yield and Safety of Thoracentesis in Hematopoietic Stem Cell Transplantation Recipients

The aim of this study was to assess the diagnostic value and safety of thoracentesis in hematopoietic stem cell transplantation (HSCT) recipients. We identified all hospitalized HSCT recipients who underwent thoracentesis from 1998 to 2006. We collected patients’ clinical characteristics, indications for thoracenstesis, the complications of the procedure, and the etiology of the pleural effusion. A total of 50 thoracentesis findings were analyzed. Twenty-six patients underwent allogeneic HSCT, while 24 patients underwent autologous HSCT. The main indications for performing thoracentesis were to rule out infection and document or diagnose malignancy. Pleural effusions were characterized as exudate in 33 patients (66%). A specific diagnosis based on the thoracentesis was made in 13 patients (26%). These were malignancy in nine patients, parapneumonic in three patients, and empyema in one patient. The only documented complication was pneumothorax in five patients. The presence of exudative effusion and underlying solid malignancy were associated with specific diagnosis by thoracentesis (p = 0.0001 and 0.013, respectively). In spite of the tendency of HSCT recipients to develop pulmonary infections, complex parapneumonic effusions are rarely diagnosed by thoracentesis. The rate of complications is comparable to other patient populations.     

Gut Toxicity During Hemopoietic Stem Cell Transplantation May Predict Acute Graft-Versus-Host Disease Severity in Patients

Graft-versus-host disease (GVHD) is the primary complication of allogeneic, hemopoietic, stem cell transplantation (HSCT). Murine models suggest that gut toxicity, induced by the intensive chemotherapy preceding hematopoietic stem cell infusion, aggravates systemic GVHD. In HSCT patients gut toxicity correlates with chemotherapy intensity. The present study investigates acute GVHD severity and intestinal toxicity in patients undergoing allogeneic HSCT. In 38 patients intestinal permeability was assessed before and after chemotherapy (on days −1, +4, +7 and +14 as related to the stem cell infusion). Cumulative acute GVHD (days 0–100) and clinical intestinal toxicity (days 0–14) were evaluated in parallel. Patients with mild, acute GVHD (grades 0–I) had better-preserved intestinal barrier function (P=0.04) and less pronounced cumulative clinical intestinal toxicity (P=0.02) compared with patients with more severe acute GVHD (grades II–IV). Gut toxicity predicts acute GVHD severity. Therefore, gut protective strategies may diminish GVHD severity in allogeneic HSCT patients.     

The use of ATG abrogates the antileukemic effect of cytomegalovirus reactivation in patients with acute myeloid leukemia receiving grafts from unrelated donors

Several studies provided evidence of a consistent antileukemic effect induced by cytomegalovirus (CMV) replication in acute myeloid leukemia (AML) patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), however the use of antithymocyte globulin (ATG) as graft‐versus‐host disease prophylaxis, may potentially abrogate the protective effect of CMV infection. To address this issue, we retrospectively analyzed the risk of relapse in a cohort of 101 patients with AML who received grafts from an unrelated donor after a conditioning regimen including ATG. The cumulative incidence of CMV reactivation, evaluated by RT qPCR, was 59% at 12 months, and 93% of CMV reactivations occurred within the first 100 days post HSCT. The 5‐year cumulative incidence of relapse in patients with CMV reactivation was 29% compared with 37% for patients without CMV reactivation, and the only factor associated with a reduced 5‐year cumulative incidence of relapse was the disease status at HSCT (P < 0.001). In the multivariable model adverse cytogenetics (HR 2.42, 95% CI 1.02‐5.72; P = 0.044) and acute GVHD (HR 3.36, 95% CI 1.32‐8.54; P = 0.011) were independent risk factors for reducing overall survival (OS), while the presence of chronic GVHD was associated with a better OS (HR 0.37, 95% CI 0.15‐0.89; P = 0.027). CMV replication was not an independent risk factor for OS (HR 1.06, 95% CI 0.07‐15.75; P = 0.965). In Conclusion, the results of present study suggest that relapse prevention in patients with AML receiving T‐cell depleted HSCT using ATG do not benefit from CMV reactivation. Am. J. Hematol. 90:E117–E121, 2015. © 2015 Wiley Periodicals, Inc.     

Long-term pattern of pleural effusion from chronic myeloid leukemia patients in second-line dasatinib therapy

Dasatinib is a potent second-generation tyrosine kinase inhibitor approved for the treatment of chronic myeloid leukemia after imatinib failure. However, some patients treated with dasatinib experience pleural effusions (PEs). The determinants of pleural effusion in long-term dasatinib treatment (median 35 months, range 1–55) were investigated in single-center data of 65 patients enrolled in global phase 2 and phase 3 trials. Of the 65 patients, 35 (54%) developed dasatinib-induced pleural effusion (a median onset time, 20 months; range 0.2–54). The first pleural effusion developed in 15 (43%) patients within 12 months of dasatinib therapy. Disease phase (P = 0.02), dose schedule (P = 0.002) and actual daily mean dose (P = 0.0002) were significantly associated with an increased risk of pleural effusion. Twice-daily administration of dasatinib resulted in significantly more patients developing pleural effusions compared with the once-daily dosing schedule, particularly in advanced disease. In addition, a strong correlation was found between actual daily mean dose and time to onset of pleural effusions in patients treated with a daily mean dose >100 mg/day of dasatinib (P = 0.01). These data emphasize the need for dasatinib dose and schedule optimization and long-term monitoring of dasatinib-treated patients to prevent the negative clinical implications of pleural effusion.     

Role of autologous hematopoietic stem cell transplantation according to the NPM1/FLT3‐ITD molecular status for cytogenetically normal AML patients: A GOELAMS study

The choice of postremission therapy for acute myeloid leukemia (AML) patients is now based on the blasts' cytogenetic and molecular profile. However, the potential benefit of autologous hematopoietic stem cell transplantation (auto‐HSCT) according to the NPM1/FLT3‐ITD status has been poorly studied in AML patients with a normal karyotype (NK). Therefore, we evaluated the NPM1/FLT3‐ITD molecular status in 135 NK‐AML patients treated by allogeneic HSCT (allo‐HSCT), auto‐HSCT, or chemotherapy as consolidation therapy within the GOELAMS LAM‐2001 trial. In univariate analyzes, 4‐year leukemia‐free survival (LFS) and overall survival (OS) were significantly higher for NPM1+/FLT3‐ITD? patients compared with patients presenting another molecular profile (61 vs. 43% and 72 vs. 48%, P = 0.02 and P = 0.01, respectively). In the NPM1+/FLT3‐ITD? subgroup, there was no benefit for allo‐HSCT or auto‐HSCT vs. chemotherapy (4‐year LFS: 71, 56, and 60%; 4‐year OS: 73, 71, and 60%, respectively; P = NS). For patients with other NPM1/FLT3‐ITD molecular profiles, allo‐HSCT was found to be the best consolidation therapy, whereas auto‐HSCT was associated with a better outcome when compared with chemotherapy (allo‐HSCT‐, auto‐HSCT‐, and chemotherapy‐related 4‐year LFS: 68, 44, and 36%, P = 0.004; 4‐year OS: 68, 52, and 29%, respectively, P = 0.02). Our study indicates that allo‐HSCT and auto‐HSCT provide similar outcomes compared with chemotherapy as consolidation for NPM1+/FLT3‐ITD? NK‐AML patients. For NK‐AML patients with an adverse molecular profile, auto‐HSCT could represent an alternative therapeutic approach when no human leukocyte antigen–matched allogeneic donor is available. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.     

Clinical outcomes of myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement

Objective: Myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement are hematopoietic stem cell disorders with a poor prognosis, but no established standard therapy. Methods: We experienced a patient with T-lymphoblastic lymphoma (LBL) associated with FGFR1 rearrangement who underwent cord blood transplantation, but died of pulmonary complication. We collected the clinical data of patients with FGFR1 rearrangement from the medical literature and analyzed 45 patients, including our patient. Results: The primary diagnoses were myeloproliferative neoplasm (MPN) or myelodysplastic syndromes (MDS) in 14 and acute leukemia or LBL in 31. In MPN and MDS patients, the cumulative incidence of transformation to blast phase (BP) at 12 months was 46.2%. The 1-year overall survival (OS) from diagnosis in all cases was 43.1%. With regard to the impact of treatment response on survival, the achievement of complete response with a landmark at 2 months after diagnosis of BP was associated with a superior OS (40.0% vs. 26.0% P?=?0.011 for 1-year OS from BP). Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 13 patients, and the 1-year OS from allogeneic HSCT was 61.5%. The hazard ratio for mortality was 0.34 (95% CI, 0.08–1.51, P?=?0.15) for allogeneic HSCT treated as a time-dependent covariate, which suggests that allogeneic HSCT may confer a clinical benefit. Conclusion: The further accumulation of clinical data is needed to determine the optimal therapeutic approach for these neoplasms.     

Pneumonia and empyema: causal,casual or unknown

Parapneumonic effusions complicating pneumonia are associated with increased morbidity and mortality. Along with increased mortality, complicated parapneumonic effusion and empyema often necessitate prolonged treatment, longer hospital stay and interventions. Parapneumonic effusions arise from inflammation in the lungs and pleural space from direct invasion of bacteria, cascade of inflammatory events and bacteriologic virulence features. Patient factors and comorbidities also contribute to the pathophysiology of parapneumonic effusion development. The evolution of parapneumonic effusion can be divided into three progressive stages: (I) exudative stage; (II) fibrinopurulent stage; and (III) organizing stage with pleural peel formation. These stages can help categorize effusions into groups in order to evaluate the risk of a complicated course requiring intervention. We recommend that clinical data be evaluated and a stepwise approach be taken in management of these patients. This review article discusses current understanding of the development and relationship of parapneumonic effusions with pneumonia.     

Charlson comorbidity index and adult comorbidity evaluation-27 scores might predict treatment compliance and development of pleural effusions in elderly patients with chronic myeloid leukemia treated with second-line dasatinib

Background

Comorbidities may affect survival and choice of treatment among cancer patients. In fact, comorbidities have been identified as significant determinants of response to therapy in older patients with acute myeloid leukemia, breast cancer, head and neck cancer, and lung cancer. The Charlson comorbidity index and adult comorbidity evaluation-27 are lists of comorbidities with a weight assigned from 1 to 6 for the former and from 0 to 3 for the latter score, derived from relative risk estimates of a proportional hazard regression model using clinical data.

Design and Methods

We retrospectively evaluated the Charlson index and adult comorbidity evaluation-27 score in a cohort of 125 elderly (> 60 years) patients with chronic phase chronic myeloid leukemia who received dasatinib after showing resistance or intolerance to imatinib with the aim of establishing associations between comorbidities and the development of pleural effusions or compliance with the drug treatment.

Results

We found a significant association between the Charlson index as well as the adult comorbidity evaluation-27 score and the rate of drug reduction or suspension: with regards to the Charlson index, 49% of score 0 patients had a dose reduction compared to 63% of patients with score 1, 74% of those with score 2 and 100% of patients with score 3–5 (P=0.03); with regards to the adult comorbidity evaluation-27 score, 45% of patients had score 0–1 and 69% of patients with score 2–3 had a dose reduction. Of the 65 patients with Charlson score 0, 29% had at least one suspension of treatment (79% for hematologic and 21% for non-hematologic toxicity), compared to 46% of patients with score 1 (37% for hematologic and 69% for non-hematologic toxicity), 58% of patients with score 2 (36% for hematologic and 64% for non-hematologic toxicity) and 100% of patients with score 3 or 4 (all patients for both types of toxicity). High adult comorbidity index-27 scores identified patients at high risk of grade 3/4 hematologic toxicity. Forty-one patients (32.8%) experienced pleural effusion during treatment: the highest scores for both indices were associated with an increased risk of pleural effusions.

Conclusions

In elderly patients with chronic myeloid leukemia treated with dasatinib, the rate of drug reduction or suspension and the incidence of pleural effusions seem to be associated with the presence of comorbidities: stratification according to the Charlson index and adult comorbidity evaluation-27 score before dasatinib therapy may enable the identification of patients at risk of major toxicities.     

Increased regulatory T cell graft content is associated with improved outcome in haematopoietic stem cell transplantation: a systematic review

Allogeneic haematopoietic stem cell transplant (HSCT) recipients are at increased risk of morbidity and mortality, often due to the development of acute or chronic graft‐versus‐host disease (GVHD). Low numbers or proportions of regulatory T cells (Tregs) have been reported in patients who develop GVHD. We undertook a systematic review of studies that reported the Treg composition of HSCT grafts in patients with haematological malignancies. Fourteen eligible studies were identified, eight of which stratified patients by Tregs (absolute dose or ratio to CD3+ or CD4+ cells). Meta‐analyses showed that high levels of Tregs in the grafts were associated with improved overall survival [hazard ratio (HR) 0·42, 95% confidence interval (CI) 0·23–0·74, P  = 0·003, 2 studies], with a significant reduction in non‐relapse mortality (HR 0·30, 95% CI 0·14–0·64, P  = 0·002, 2 studies) and a reduced risk of acute GVHD (relative risk (RR) 0·59, 95% CI 0·40–0·89, P  = 0·01, 6 studies). The consistency of these findings strongly suggests that the Treg composition of HSCT grafts has a powerful effect on the success of allogeneic HSCT. The major challenge is to translate these findings into better selection of allografts and future donors to provide a substantial improvement in allogeneic HSCT outcomes and practice.     

Allogeneic bone marrow vs. peripheral blood stem cell transplantation: a long-term retrospective single-center analysis in 329 patients

Objectives: Granulocyte colony‐stimulating factor‐mobilized peripheral blood hematopoietic stem cell transplantation (HSCT) provides a valuable and increasingly used alternative to bone marrow transplantation (BMT). This retrospective study aimed at determining whether the stem cell source is predictive for outcome, relapse incidence, non‐relapse mortality, and severity and incidence of both, acute and chronic graft‐versus‐host disease (GVHD) in patients undergoing allogeneic HSCT. Patients and methods: Between 1983 and 2007, 329 adult patients (median age 40, range 18–76) received a first allogeneic HSCT from either sibling (n = 203) or volunteer unrelated donors (n = 126) at our institution. The source of stem cells was bone marrow in 177 (54%) and peripheral blood in the remaining 152 (46%) patients. Results: Overall survival was 37% (31–43%, 95% confidence interval, CI), the relapse incidence was 30% (25–36%, 95% CI), and the non‐relapse mortality was 43% (38–49%, 95% CI) for the entire cohort with no significant differences between peripheral blood stem cell or BMT. In patients receiving myeloablative conditioning, peripheral blood stem cell transplantation (PBSCT) was associated with a significantly lower non‐relapse mortality (32% vs. 46%, P = 0.05), which, however, was restricted to standard‐risk disease (23% vs. 42%, P = 0.02). The overall cumulative incidences of acute GVHD II–IV were 51% and 54% following bone marrow and PBSCT, respectively. Severe acute GVHD III–IV was significantly more frequent after BMT (24% vs. 14%, P = 0.04), whereas chronic GVHD was significantly more frequent following PBSCT (48% vs. 24%, P = 0.0001). By multivariate analysis, PBSCT was only predictive for chronic GVHD (RR 2.29, P = 0.02). Conclusion: Although we failed to demonstrate any advantage of PBSCT over conventional BMT with regard to overall survival, relapse incidence and non‐relapse mortality PBSCT were associated with a significantly higher incidence of chronic graft‐versus‐host disease. Therefore, and by virtue of observations, that some patient groups might benefit from either stem cell source, there is still need for prospective randomized trials with special emphasize on quality of life in long‐term survivors.     

Allogeneic transplantation is not superior to chemotherapy in most patients over 40 years of age with Philadelphia‐negative acute lymphoblastic leukemia in first remission

Survival of patients ≥40 years of age with Philadelphia‐negative acute lymphoblastic leukemia (ALL) remains poor with current therapeutic approaches. It is unknown whether allogeneic hematopoietic stem‐cell transplantation (HSCT) in first remission confers a survival benefit compared to a chemotherapy‐only approach. We retrospectively compared the outcome of patients >40 years treated with HSCT or chemotherapy alone in first remission (n = 40 in each cohort). Three‐year overall survival (OS) and disease‐free survival (DFS) were not significantly different between the chemotherapy‐only and HSCT groups (OS, 46% [31–68] vs. 40% [27–59], P = 0.35; DFS, 31% [18–52] vs. 40% [27–59], P = 0.98). The 3‐year cumulative incidence of relapse (CIR) and non‐relapse mortality (NRM) were 61% [41–76] and 9% [2–21] for the chemotherapy‐only group and 28% [15–43] and 32% [17–47] for the transplant group (CIR, P = 0.011; NRM, P = 0.014). Allogeneic transplantation for patients ≥40 years with Ph‐negative ALL in first remission is associated with a lower CIR, but this benefit is offset by considerable NRM as compared with chemotherapy‐only approach. HSCT may be beneficial in patients with high‐risk disease features. Am. J. Hematol. 91:793–799, 2016. © 2016 Wiley Periodicals, Inc.     

The addition of sirolimus to the graft‐versus‐host disease prophylaxis regimen in reduced intensity allogeneic stem cell transplantation for lymphoma: a multicentre randomized trial

Inhibition of the mechanistic target of rapamycin (mTOR) pathway has clinical activity in lymphoma. The mTOR inhibitor sirolimus has been used in the prevention and treatment of graft‐versus‐host disease (GVHD) after allogeneic haematopoietic stem cell transplantation (HSCT). A retrospective study suggested that patients with lymphoma undergoing reduced intensity conditioning (RIC) HSCT who received sirolimus as part of their GVHD prophylaxis regimen had a lower rate of relapse. We therefore performed a multicentre randomized trial comparing tacrolimus, sirolimus and methotrexate to standard regimens in adult patients undergoing RIC HSCT for lymphoma in order to assess the possible benefit of sirolimus on HSCT outcome. 139 patients were randomized. There was no difference overall in 2‐year overall survival, progression‐free survival, relapse, non‐relapse mortality or chronic GVHD. However, the sirolimus‐containing arm had a significantly lower incidence of grade II‐IV acute GVHD (9% vs. 25%, P = 0·015), which was more marked for unrelated donor grafts. In conclusion, the addition of sirolimus for GVHD prophylaxis in RIC HSCT is associated with no increased overall toxicity and a lower risk of acute GVHD, although it does not improve survival; this regimen is an acceptable option for GVHD prevention in RIC HSCT. This trial is registered at clinicaltrials.gov (NCT00928018).     

Outcome of aplastic anaemia in children. A study by the severe aplastic anaemia and paediatric disease working parties of the European group blood and bone marrow transplant

This study analysed the outcome of 563 Aplastic Anaemia (AA) children aged 0–12 years reported to the Severe Aplastic Anaemia Working Party database of the European Society for Blood and Marrow Transplantation, according to treatment received. Overall survival (OS) after upfront human leucocyte antigen‐matched family donor (MFD) haematopoietic stem cell transplantation (HSCT) or immunosuppressive treatment (IST) was 91% vs. 87% (P 0·18). Event‐free survival (EFS) after upfront MFD HSCT or IST was 87% vs. 33% (P 0·001). Ninety‐one of 167 patients (55%) failed front‐line IST and underwent rescue HSCT. The OS of this rescue group was 83% compared with 91% for upfront MFD HSCT patients and 97% for those who did not fail IST up‐front (P 0·017). Rejection was 2% for MFD HSCT and HSCT post‐IST failure (P 0·73). Acute graft‐versus‐host disease (GVHD) grade II‐IV was 8% in MFD graft vs. 25% for HSCT post‐IST failure (P < 0·0001). Chronic GVHD was 6% in MFD HSCT vs. 20% in HSCT post‐IST failure (P < 0·0001). MFD HSCT is an excellent therapy for children with AA. IST has a high failure rate, but remains a reasonable first‐line choice if MFD HSCT is not available because high OS enables access to HSCT, which is a very good rescue option.     

Optimal management of chronic graft‐versus‐host disease in children

Chronic graft‐versus‐host disease (GVHD) is a major complication after allogeneic haematopoietic stem cell transplantation (HSCT). Not only is it the major cause of late mortality in HSCT patients, but it also accounts for significant morbidity. Much of the literature on chronic GVHD has focused on adults. Chronic GVHD is of major importance in children, especially since they have years to live following the complications of chronic GVHD and its therapy. The goal is to review incidence, manifestations, and therapies, especially when applicable to the paediatric population.     

The hematopoietic cell transplantation‐specific comorbidity index (HCT‐CI) is an outcome predictor for partially matched related donor transplantation

To validate the predictive ability of the Hematopoietic Cell Transplantation‐Specific Comorbidity Index (HCT‐CI) on the outcome of hematopoietic stem cell transplantation (HSCT) patients who received transplants from partially matched related donors (PMRD), a total of 526 patients who received PMRD HSCT between January 2006 and December 2009 at the Institute of Hematology, Peking University were enrolled. Patients were grouped according to their HCT‐CI score; 31.0%, 31.4%, and 37.6% of patients had HCT‐CI scores of 0, 1–2, and ≥3, respectively. Patients with HCT‐CI scores of ≥3 had a significantly poorer 2‐year overall survival (OS) than patients with HCT‐CI scores of 0–2 (54.55% vs. 78.05%, P < 0.001). In addition, patients with HCT‐CI scores of ≥3 had a significantly higher 2‐year cumulative incidence of relapse and nonrelapse mortality (NRM) than patients with scores of 0–2 (relapse: 23.23% vs. 11.59%, P < 0.001; NRM: 34.30% vs. 15.93%, P < 0.001). HCT‐CI scores of <3 were associated with better OS, less relapse, and lower NRM in multivariate analysis. Patients who had high comorbidity scores as well as high‐risk disease had the poorest outcomes. Therefore, we found that HCT‐CI is associated with the outcomes of PMRD HSCT and we should closely monitor patients with a high comorbidity burden. Am. J. Hematol. 88:497–502, 2013. © 2013 Wiley Periodicals, Inc.     

Tacrolimus instead of cyclosporine used for prophylaxis against graft-versus-host disease improves outcome after hematopoietic stem cell transplantation from unrelated donors, but not from HLA-identical sibling donors: a nationwide survey conducted in Japan

Despite recent advances, graft-versus-host disease (GVHD) remains the main cause of treatment failure for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Tacrolimus (FK506) has been increasingly used in place of cyclosporine (CSP), and several studies have shown that FK506 reduces the incidence of acute GVHD more effectively than does CSP. However, no survival benefits have been demonstrated, and no established consensus exists on the choice of these immunosuppressive agents. To compare a CSP-based and an FK506-based regimen, we performed a large-scale retrospective study by using the data of 1935 patients who underwent HSCT from HLA-identical sibling donors (SIB-HSCT) and 777 patients who underwent HSCT from unrelated donors (UD-HSCT). For patients undergoing UD-HSCT, FK506 significantly reduced the risk of acute GVHD and treatment-related mortality (TRM) without an increase in relapse, thus improving overall survival (OS) (hazard ratio (HR): 2.20, 95% confidence interval (CI): 1.60-3.04, P<0.0001 for grade II-IV acute GVHD; HR: 1.81, 95% CI: 1.32-2.48, P=0.0003 for TRM; HR: 1.62, 95% CI: 1.23-2.14, P=0.0007 for OS). This superiority of FK506 was not observed in SIB-HSCT cases. These findings indicate that the use of FK506 instead of CSP for GVHD prophylaxis is beneficial for patients undergoing UD-HSCT.     

A conditioning platform based on fludarabine,busulfan, and 2 days of rabbit antithymocyte globulin results in promising results in patients undergoing allogeneic transplantation from both matched and mismatched unrelated donor

Conditioning regimen including fludarabine, intravenous busulfan (Bx), and 5 mg/kg total dose of rabbit antithymocyte globulin (r‐ATG) (FBx‐ATG) results in low incidence of graft‐versus‐host disease (GVHD) and non‐relapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (Allo‐HSCT) from HLA‐matched related or unrelated donors (MUD). However, whether this platform produces similar results in the setting of one mismatch unrelated donor (MMUD) Allo‐HSCT is not known. We retrospectively analyzed patients aged less than 65 years who were diagnosed with hematological malignancies and received FBx‐ATG regimen prior to Allo‐HSCT from MUD (N = 74) or MMUD (N = 40). We compared outcome of MUD versus MMUD patients. There was no difference in the cumulative incidence of grades II–IV acute GVHD (MUD: 34% vs. MMUD: 35%, P = 0.918), but MMUD patients developed more grade III–IV acute GVHD (MUD: 5% vs. MMUD: 15%, P = 0.016). The cumulative incidences of overall chronic GVHD (MUD: 33% vs. MMUD: 22%, P = 0.088) and extensive chronic GVHD (MUD: 20% vs. MMUD: 19%, P = 0.594) were comparable. One‐year NRM was similar in both groups (MUD: 16% vs. MMUD: 14%, P = 0.292); similarly, progression‐free survival (MUD: 59% vs. MMUD: 55%, P = 0.476) and overall survival (MUD: 63% vs. MMUD: 61%, P = 0.762) were not different between both groups. With a median follow up of 24 months, 35 of 74 MUD patients (47%) and 19 of 40 MMUD patients (48%) were free of both disease progression and immunosuppressive treatment. We conclude that the FBx‐ATG regimen results in low incidences of NRM and GVHD in both MUD and the MMUD recipients. Am. J. Hematol. 89:83–87, 2014. © 2013 Wiley Periodicals, Inc.     

Persistent symptomatic pleural effusion following coronary bypass surgery: clinical and histologic features,and treatment

Pleural effusions following coronary artery bypass grafting (CABG) have been reported in 65%–89% of the cases. The majority of pleural effusions are left-sided, of little significance, and resolve spontaneously. However, a few pleural effusions require specific therapeutics. We report clinical and pleural histologic features of three patients who had persistent post-CABG pleural effusions and underwent video-assisted thoracic surgery (VATS). These patients were studied because they had a persistent pleural effusion within the first 2 months after CABG without other identifiable causes. All patients underwent VATS for investigation and management of persistent pleural effusions. Three patients with a mean age of 63.6 ± 8.5 years were studied. The pleural effusion developed 38 ± 11.3 days after CABG (range: 22–46). The median period from CABG to VATS was 80 ± 21.6 days (range: 50–100). In all cases, the pleural effusion was large, and predominated on the left side. Pleural effusions were characterized by an exudative (n = 2) or transudative (n = 1) fluid with lymphocytosis. Histologic examination of pleural biopsies showed a follicular lymphoid hyperplasia involving the pleural serosa and a non-necrotizing granulomatous reaction with a mild inflammatory infiltrate. All patients underwent VATS with intrapleural injection of sclerosing agents. Video-assisted thoracic surgery talc pleurodesis led to symptomatic and radiologic improvement in all patients with a mean follow-up of 16.7 ± 4.5 months. No recurrence of pleural effusion has been observed in any patient. Large pleural effusions can develop in a small proportion of patients after CABG. The mechanism of pleural effusion remains unclear. Video-assisted thoracic surgery could play a significant role in the management of pleural effusion developing after CABG.     

Donor compatibility and performance status affect outcome of allogeneic haematopoietic stem cell transplant in patients with relapsed or refractory acute myeloid leukaemia

We retrospectively analysed 78 patients with relapsed (n?=?38), primary refractory (n?=?34) or untreated (n?=?6) acute myeloid leukaemia (AML) who underwent allogeneic HSCT at our Institution between 2002 and 2011, to verify outcome and to identify factors that can affect long-term outcome. Myeloablative conditioning regimens were used in 48 patients (24 siblings, 24 matched unrelated donor (MUD)), while 30 patients (18 siblings, 12 MUD) received reduced-intensity conditioning. Acute graft versus host disease (GVHD) developed in 37 (47?%) patients, while chronic GVHD occurred in 19 of the 65 evaluable patients (29?%). With a median follow-up time of 5?years, 13 of 78 patients (17?%) are alive and in complete remission (CR), while 64 have died. Cause of death was disease recurrence in 37 patients (58?%), infection in ten patients (16?%) and GVHD in six (9?%). One-year non-relapse mortality was 35?%. In multivariate analysis, performance status ≥80?% WHO and a full-matched donor were associated with a better outcome: these two variables allowed for risk stratification, identifying three groups with significantly different survival after transplant (P?=?0.0001). Considering post-transplant variables, only CR at recovery and development of cGVHD were correlated with a longer survival. Our data confirm the capacity of allogeneic transplant to prolong survival in a significant proportion of extremely high-risk AML patients.     

Pleural effusion in patients with pulmonary embolism

Background and objective: It has been suggested that pulmonary embolism (PE) is an under‐recognized cause of pleural effusion. This study aimed to (i) establish the incidence and clinical relevance of pleural effusion in patients with pulmonary emboli; and (ii) determine if there is a relationship between development of pleural effusions and the location of emboli and number of pulmonary arteries involved. Methods: A retrospective analysis of all CT pulmonary angiograms (CTPA) performed over 12 months on adult patients with clinically suspected PE in a hospital which used CTPA as first‐line imaging investigation for PE. Results: Of 285 CTPA, 60 patients (21%) had evidence of pulmonary emboli (38 had both central and peripheral clots and 22 peripheral emboli only). Emboli were bilateral in 39 cases and unilateral in 21 cases. Pleural effusion was present in almost one half (n = 29, 48%) of the patients with pulmonary emboli. Patients with pulmonary emboli were more likely to have a pleural effusion (OR 2.2 (95% CI: 1.1–4.7), P < 0.05) than patients without PE; however, the effusions were generally very small. Most (86%) of the effusions were present on the same side as the emboli. The location of emboli and number of arteries involved did not predict the presence of pleural effusions. Conclusions: Pleural effusion is common in patients with pulmonary emboli demonstrated on CTPA. These effusions are small and seldom alter clinical management. Clinicians should therefore have a high threshold of suspicion in attributing large or contralateral pleural effusions to embolic diseases without excluding alternative diagnoses.