Summary
Outcome of 333 children with acute myeloid leukaemia relapsing after a first allogeneic haematopoietic stem cell transplantation was analyzed. Four‐year probability of overall survival ...(4y‐pOS) was 14%. 4y‐pOS for 122 children receiving a second haematopoietic stem cell transplantation was 31% and 3% for those that did not (P = <0·0001). Achievement of a subsequent remission impacted survival (P = <0·0001). For patients receiving a second transplant survival with or without achieving a subsequent remission was comparable. Graft source (bone marrow vs. peripheral blood stem cells, P = 0·046) and donor choice (matched family vs. matched unrelated donor, P = 0·029) positively impacted survival after relapse. Disease recurrence and non‐relapse mortality at four years reached 45% and 22%.
Background
Results have been varied regarding the effect of donor age on the outcome of unrelated donor haemopoietic cell transplantation (HCT).
Aims
To determine the influence of donor age on adult ...unrelated donor HCT outcome in Australia.
Methods
Patients were included in the study if they were aged 16 years or above and underwent first allogeneic unrelated donor HCT in Australia for the indications of acute lymphoblastic leukaemia (ALL), acute myelogenous leukaemia (AML), chronic myelogenous leukaemia (CML) or myelodysplastic syndromes (MDS) between the years of 2001 and 2014 inclusive. The main outcome measure was overall survival (OS), which was tested against independent variables using univariate Kaplan–Meier methods and multivariate Cox regression.
Results
A total of 1158 unrelated donor HCT were represented in the data. Cumulative incidences of engraftment, transplant related mortality (TRM), acute graft‐versus‐host disease (GvHD), chronic GvHD and relapse were not significantly affected by donor age. OS probability at 5 years post‐transplant was 48.3%. In multivariate analysis of OS, year of transplant 2001–2007, recipient age 40 years or greater, poor risk disease, human leukocyte antigen (HLA) match less than 6/6 and poor performance status at transplant (Karnofsky scale) were independently significant adverse OS risk factors. Donor age was not a significant risk factor for OS in univariate or multivariate analysis.
Conclusions
The conclusion from this study was that donor age (up to 59 years) did not influence post‐transplant outcome among adult unrelated donor HCT performed in Australia for haematologic malignancies.
Aim
High dose melphalan (HDM) and autologous stem cell transplantation (ASCT) retains a central role in the treatment of myeloma. The aim of this study was to determine whether HDM exposure (area ...under the concentration vs. time curve, AUC), is significantly associated with transplant outcomes.
Methods
Melphalan concentrations were measured in six to 11 plasma samples collected after HDM (median 192 mg m–2) to determine melphalan AUC for a total of 114 patients. Binary logistic regression was used to assess whether melphalan AUC was associated with severe (≥ grade 3) oral mucositis. Multivariate Cox regression was used to assess whether melphalan AUC was significantly associated with time to progression, progression‐free survival and overall survival (OS).
Results
Melphalan AUC ranged from 4.9 to 24.6 mg l–1 h, median 12.84 mg l–1 h. Melphalan AUC above the median was a risk factor for severe mucositis (HR 1.21, 95% CI 1.06, 1.38, P = 0.004) but was also associated with significantly improved overall survival (OS) (HR 0.40, 95% CI 0.20, 0.81, P = 0.001), with an estimated median survival of 8.50 years vs. 5.38 years for high vs. low AUC groups. Multivariate analysis did not identify melphalan AUC as being significantly associated with time to progression or progression‐free survival.
Conclusions
This large scale pharmacodynamic analysis of HDM demonstrates that high melphalan exposure is associated with improved survival, with an acceptable increase in transplant toxicity. These results suggest studies targeting a higher AUC are warranted in patients undergoing HDM and ASCT for myeloma.
Background
Approximately one‐third of children with acute myeloid leukemia (AML) relapse, requiring re‐treatment and allogeneic hematopoietic stem cell transplantation (HSCT). Although achieving ...second complete remission (CR2) prior to HSCT is desirable, once CR2 is attained, it is unclear if there is any benefit from further chemotherapy prior to HSCT. Moreover, although pre‐HSCT minimal residual disease (MRD) has prognostic value in acute lymphoblastic leukemia, the benefit of MRD reduction after achieving CR prior to HSCT is less clear for AML.
Procedure
To address these questions, we analyzed data from pediatric transplant centers in Australia and New Zealand concerning relapsed childhood AML cases occurring between 1998 and 2013. Given the retrospective nature of our analysis and assay data available, we analyzed patients on the basis of measurable residual disease (MeRD) by any methodology, rather than MRD in the conventional sense.
Results
We observed improved overall survival (OS) in children receiving two chemotherapy cycles, compared to one cycle or three or more cycles pre‐HSCT. Improved OS with two cycles remained significant for patients without MeRD after cycle 1.
Conclusions
These data suggest that a second chemotherapy cycle pre‐HSCT may improve survival by lowering disease burden. Prospective trials assessing strategies to reduce pre‐HSCT MRD in relapsed childhood AML are warranted.
Background
Extracorporeal membrane oxygenation (ECMO) provides support to patients with severe but reversible cardiac or pulmonary failure. Vascular complications of ECMO are well recognized.
Methods
...We performed a retrospective review of 70 patients (mean age 48 years; 15–85) who received peripheral veno‐arterial ECMO from 2004 to 2010 in a single centre. For statistical analysis, chi‐squared test and multivariate binary logistic regression analysis were used to assess for association between response variables (i.e. limb ischaemia, ECMO site bleeding and deep vein thrombosis (DVT)) and possible predictive variables.
Results
There were 14 (20%) cases of acute limb ischaemia with no statistically significant relationship between acute limb ischaemia and independent variables. Thirty‐three patients received distal limb cannulas (47%). There was no statistically significant association between limb ischaemia and presence of distal limb cannula (P = 0.8). Multivariate binary logistic regression analysis identified insertion by cutdown as a predictor of lower probability of insertion site bleeding (n = 12, odds ratio 0.24, P = 0.04). Seven cases of DVT were identified; multivariate binary logistic regression analysis identified insertion by cutdown (odds ratio 0.08, P = 0.03) and days of ECMO less than five (odds ratio 0.08, P = 0.04) as predictive factors for reduced rates of DVT.
Conclusion
Ischaemic complications of ECMO are common and occur despite the presence of a distal limb‐perfusing cannula; however in our study the distal limb cannula was a limb‐salvaging intervention in six patients. Prolonged time on ECMO is a risk factor for DVT, and a high index of suspicion must be maintained. Percutaneous insertion was associated with higher rates of bleeding and DVT.
This study characterized the contribution of bone marrow-derived cells to human neoplasia and the perineoplastic stroma. The Australasian Bone Marrow Transplant Recipient Registry was used to ...identify solid organ neoplasia that developed in female recipients of male allogeneic stem cell transplants. Eighteen suitable cases were identified including several skin cancers, two gastric cancers, and one rectal adenoma. Light microscopy, fluorescence and chromogenic in situ hybridization, and immunohistochemistry were performed to determine the nature and origin of the neoplastic and stromal cells. In contrast to recent reports, donor-derived neoplastic cells were not detected. Bone marrow-derived neoplasia-associated myofibroblasts, however, were identified in the rectal adenoma and in a gastric cancer. Bone marrow-derived cells can generate myofibroblasts in the setting of human gastrointestinal neoplasia.
Between 2005 and 2015, 138,165 hematopoietic stem cell transplantation (HSCT) were reported in 18 countries/regions in the Asia-Pacific region. In this report, we describe current trends in HSCT ...throughout the Asia-Pacific region and differences among nations in this region and various global registries. Since 2008, more than 10,000 HSCTs have been recorded each year by the Asia-Pacific Blood and Marrow Transplantation Group Data Center. Between 2005 and 2015, the greatest increase in the number of HSCTs was observed in Vietnam. Allogeneic HSCT was performed more frequently than autologous HSCT, and a majority of cases involved related donors. Regarding allogeneic HSCT, the use of cord blood has remained steady, especially in Japan, and the number of cases involving related HLA non-identical donors has increased rapidly, particularly in China. The incidence of hemoglobinopathy, a main indication for allogeneic HSCT in India, China, Iran, and Pakistan, increased nearly six-fold over the last decade. Among the 18 participating countries/regions, the transplant rate per population varied widely according to the absolute number of HSCTs and the national/regional population size. We believe that this report will not only benefit the AP region but will also provide information about HSCT to other regions worldwide.
Heart and lung transplant recipients have among of the highest incidence rates of post-transplant lymphoproliferative disease (PTLD). Despite this, there is a paucity of data specific to this group. ...We collated data on heart, lung and heart-lung transplant recipients with PTLD to identify disease features and prognostic factors unique to this group of patients.
Seventy cases of PTLD were identified from a single institution (41 heart, 22 lung, 6 heart-lung and 1 heart-kidney transplant) from 1984 to 2013. Demographics, immunosuppression, treatment, response, complications and survival data were analyzed. Uni- and multivariate Cox regression analyses were performed to identify prognostic factors.
The incidence of PTLD was 7.59% in heart-lung, 5.37% in heart and 3.1% in lung transplant recipients. Extranodal disease (82%) with diffuse large B-cell lymphoma (72%) was the most common presentation. Bone marrow involvement (13%) and central nervous system disease (3%) were uncommon. Heart transplant recipients had later onset of PTLD (>1 year post-transplant), with less allograft involvement, compared with lung and heart-lung recipients. Poor prognostic markers were bone marrow involvement (HR 6.75, p < 0.001) and serum albumin <30 g/liter (HR 3.18, p = 0.006). Improved survival was seen with a complete response within 3 months of treatment (HR 0.08, p < 0.001). Five-year overall survival was 29%.
This analysis is the largest to date on PTLD in heart and lung transplant recipients. It provides a detailed analysis of the disease in this group of patients and identifies unique prognostic features to aid risk stratification and guide treatment allocation.
Background
Hematopoietic stem cell transplantation (HSCT) is a life‐saving procedure for children with a variety of non‐malignant conditions. However, these children face an increased risk of late ...death and incident cancers after HSCT, which may occur many years after their initial HSCT.
Procedure
We examined cancer occurrence and late mortality in a population‐based cohort of 318 Australian children who underwent allogeneic HSCT for non‐malignant disease. Standardized incident ratios (SIRs) and standardized mortality ratios (SMRs) were calculated and compared with population controls.
Results
We identified six (1.9%) cancers at a median 9.2 years post‐HSCT. Cancer occurred 15 times more frequently than in the general population (SIR 15.4, 95% CI = 6.9–34.2). Of the 198 patients who survived for at least 2 years post‐HSCT, 11 (5.6%) died at a median 7.5 years post‐HSCT. The mortality rate was 17 times higher than in the general population (SMR 17.5, 95% CI = 9.7–31.2).
Discussion
Children transplanted for non‐malignant conditions require evidence‐based survivorship programs to reduce excess morbidity and mortality.
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