Publications by authors named "Ian Nivison-Smith"

27 Publications

  • Page 1 of 1

Effect of donor age on adult unrelated donor hematopoietic cell transplant outcome: the Australian experience.

Intern Med J 2020 Nov 1. Epub 2020 Nov 1.

Integrated Haematology Service, Royal Melbourne Hospital, Parkville, Victoria, Australia.

Background: Results have been varied regarding the effect of donor age on the outcome of unrelated donor hematopoietic cell transplantation (HCT).

Aims: This study sought 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 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 1,158 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, 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 hematologic malignancies. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.15128DOI Listing
November 2020

Hematopoietic Stem Cell Transplant Recipients Surviving at Least 2 Years from Transplant Have Survival Rates Approaching Population Levels in the Modern Era of Transplantation.

Biol Blood Marrow Transplant 2020 09 16;26(9):1711-1718. Epub 2020 Mar 16.

Department of Haematology and SCT, St Vincent's Hospital, Darlinghurst, New South Wales, Australia. Electronic address:

The health and outcomes of long-term survivors after hematopoietic cell transplant (HCT) are areas of evolving interest as short-term transplant outcomes improve. Because recent changes in transplant practice have likely changed the survivor population, we sought to assess the survival of a contemporary cohort of patients who were alive and free of disease 2 years after HCT. Data were extracted from first transplants documented between 2002 and 2011 in the Australasian Bone Marrow Transplant Recipient Registry on patients who received an allogeneic HCT for acute myeloid leukemia (AML), acute lymphoblastic leukemia, chronic myeloid leukemia (CML), non-Hodgkin lymphoma, and myelodysplastic syndromes or an autologous HCT for myeloma or lymphoma. Patients were included if they had survived at least 2 years without disease relapse or progression. Mortality rates were compared with standard Australian and New Zealand populations using relative-survival analysis. A total of 1562 allogeneic and 3822 autologous HCT patients were included, with a median follow-up of 5.6 years. Compared with a matched group of patients from our previous study from 1992 to 2001, the contemporary cohort of allogeneic HCT recipients was older and more likely to receive peripheral blood stem cells and from unrelated donors. Allogeneic HCT for AML increased, wheresa transplants for CML fell from 32% to 8%. Increasing use of reduced-intensity conditioning and unrelated donors was also seen. Long-term survival after allogeneic and autologous HCT were very similar to the previous 1992 to 2001 cohort despite changes in practice over time. Recipients of autologous HCT for myeloma demonstrated substantially lower overall survival than HCT for other indications with no clear plateau. Annual relative survival for survivors of allogeneic HCT was 96% to 99% of the general population but only 89% to 96% of the general population for recipients of autologous HCT. Late deaths were primarily due to nonrelapse causes after allogeneic HCT, but relapse or disease progression remained prominent for recipients of autologous HCT, particularly for myeloma. The management of late HCT effects is important to improve long-term survival of transplant recipients but should be tailored to the risks specific to the primary disease and transplant type. Future planning should account for the impact of the expected increase in transplant activity and number of survivors on resource utilization.
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http://dx.doi.org/10.1016/j.bbmt.2020.03.005DOI Listing
September 2020

Outcome of children relapsing after first allogeneic haematopoietic stem cell transplantation for acute myeloid leukaemia: a retrospective I-BFM analysis of 333 children.

Br J Haematol 2020 05 3;189(4):745-750. Epub 2020 Feb 3.

Division of Pediatric Hematology and Oncology, Department of Pediatrics, Universities of Medical University Hannover, Hannover, Germany.

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%.
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http://dx.doi.org/10.1111/bjh.16441DOI Listing
May 2020

Hematopoietic stem cell transplantation for children with acute myeloid leukemia in second remission: A report from the Australasian Bone Marrow Transplant Recipient Registry and the Australian and New Zealand Children's Haematology Oncology Group.

Pediatr Blood Cancer 2019 08 20;66(8):e27812. Epub 2019 May 20.

The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, Australia.

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.
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http://dx.doi.org/10.1002/pbc.27812DOI Listing
August 2019

Advances in hematopoietic stem cell transplantation in the Asia-Pacific region: the second report from APBMT 2005-2015.

Bone Marrow Transplant 2019 12 14;54(12):1973-1986. Epub 2019 May 14.

Japanese Data Center for Hematopoietic Cell Transplantation (JDCHCT), Nagoya, Japan.

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.
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http://dx.doi.org/10.1038/s41409-019-0554-9DOI Listing
December 2019

Activity and Capacity Profile of Transplant Physicians and Centers in Australia and New Zealand.

Biol Blood Marrow Transplant 2018 01 28;24(1):169-174. Epub 2017 Sep 28.

Department of Haematology and BMT, Royal Melbourne Hospital, Parkville Victoria, Australia.

We conducted a study to analyze and report on indicators of hematopoietic cell transplant (HCT) physician time use and HCT center output measures. HCT centers in Australia and New Zealand (A&NZ) were invited to provide demographic and time use details for physicians participating in HCT patient care (HCT physicians). Resource details for adult and pediatric centers were included. From a total of 46 centers that were invited to participate, completed data were received from 37 centers (80%) representing 185 HCT physicians, with a median age of 48 (range, 33 to 72), of whom 31% were women. Just over half of HCT physicians cited prior work experience in large overseas HCT centers (97, 52%) and over one-third (79, 43%) possessed postgraduate qualifications other than specialist training. Total annual mean HCTs per HCT physician full-time equivalent (FTE) were 14.2 for centers performing both allogeneic and autologous HCT, 6.6 for autologous only centers, and 10.6 for all centers. For all HCT physicians surveyed the mean proportion of time spent on HCT related tasks was 31.7%. In A&NZ, for centers that perform both allografts and autografts, there was a mean of 4.0 allogeneic HCT annually per HCT bed, compared with 2.6 for the United States and 7.1 allogeneic HCT annually per HCT physician FTE (United States, 6.3). Projections of the A&NZ HCT physician workforce indicated that the numbers of HCT physicians are likely to stay within the region of 170 to 190 for the next 10 years, whereas HCT activity will likely continue to climb steadily. Healthcare and government authorities should be prepared to enable and support greater HCT activity in A&NZ in the future.
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http://dx.doi.org/10.1016/j.bbmt.2017.09.011DOI Listing
January 2018

Graft Transit Time Has No Effect on Outcome of Unrelated Donor Hematopoietic Cell Transplants Performed in Australia and New Zealand: A Study from the Australasian Bone Marrow Transplant Recipient Registry.

Biol Blood Marrow Transplant 2017 01 4;23(1):147-152. Epub 2016 Oct 4.

Clinical Haematology and Bone Marrow Transplant Service, Royal Melbourne Hospital, Parkville, Victoria, Australia.

A previous study found that platelet recovery and mortality were worse in recipients of myeloablative bone marrow transplants where graft transit times were longer than 20 hours. This retrospective study of unrelated myeloablative allogeneic transplantation performed within Australia and New Zealand analyzed transplant outcomes according to graft transit times. Of 233 assessable cases, 76 grafts (33%) were sourced from bone marrow (BM) and 157 (67%) from peripheral blood. Grafts sourced from Australia and New Zealand (47% of total) were associated with a median transit time of 6 hours versus 32 hours for overseas sourced grafts (53% of total). Graft transit temperature was refrigerated in 85%, ambient in 6%, and unknown in 9% of cases, respectively. Graft transit times had no significant effect on neutrophil or platelet engraftment, treatment-related mortality, overall survival, and incidence of acute or chronic graft-versus-host disease. Separate analysis of BM grafts, although of reduced power, also showed no significant difference in either neutrophil or platelet engraftment or survival between short and longer transport times. This study gives reassurance that both peripheral blood stem cell and especially BM grafts subjected to long transit times and transported at refrigerated temperatures may not be associated with adverse recipient outcomes.
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http://dx.doi.org/10.1016/j.bbmt.2016.09.026DOI Listing
January 2017

Reduced intensity conditioned allograft yields favorable survival for older adults with B-cell acute lymphoblastic leukemia.

Am J Hematol 2017 Jan 12;92(1):42-49. Epub 2016 Nov 12.

CIBMTR (Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.

Older adults with B-cell acute lymphoblastic leukemia (B-ALL) have poor survival. We examined the effectiveness of reduced intensity conditioning (RIC) hematopoietic cell transplant (HCT) in adults with B-ALL age 55 years and older and explored prognostic factors associated with long-term outcomes. Using CIBMTR registry data, we evaluated 273 patients (median age 61, range 55-72) with B-ALL with disease status in CR1 (71%), >CR2 (17%) and Primary Induction Failure (PIF)/Relapse (11%), who underwent RIC HCT between 2001 and 2012 using mostly unrelated donor (59%) or HLA-matched sibling (32%). Among patients with available cytogenetic data, the Philadelphia chromosome (Ph+) was present in 50%. The 3-year cumulative incidences of nonrelapse mortality (NRM) and relapse were 25% (95% confidence intervals (CI): 20-31%) and 47% (95% CI: 41-53%), respectively. Three-year overall survival (OS) was 38% (95% CI: 33-44%). Relapse remained the leading cause of death accounting for 49% of all deaths. In univariate analysis, 3 year risk of NRM was significantly higher with reduced Karnofsky performance status (KPS <90: 34% (95% CI: 25-43%) versus KPS ≥90 (18%; 95% CI: 12-24%, P = 0.006). Mortality was increased in older adults (66+ vs. 55-60: Relative Risk [RR] 1.51 95% CI: 1.00-2.29, P = 0.05) and those with advanced disease (RR 2.13; 95% CI: 1.36-3.34, P = 0.001). Survival of patients in CR1 yields 45% (95% CI: 38-52%) at 3 years and no relapse occurred after 2 years. We report promising OS and acceptable NRM using RIC HCT in older patients with B-ALL. Disease status in CR1 and good performance status are associated with improved outcomes. Am. J. Hematol. 92:42-49, 2017. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ajh.24575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167625PMC
January 2017

Incident cancers and late mortality in Australian children treated by allogeneic stem cell transplantation for non-malignant diseases.

Pediatr Blood Cancer 2017 01 26;64(1):197-202. Epub 2016 Sep 26.

Kids Cancer Centre, Sydney Children's Hospital, Randwick, Australia.

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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http://dx.doi.org/10.1002/pbc.26219DOI Listing
January 2017

Does a distal perfusion cannula reduce ischaemic complications of extracorporeal membrane oxygenation?

ANZ J Surg 2016 Dec 28;86(12):1002-1006. Epub 2016 Feb 28.

St Vincent's Hospital, Darlinghurst, New South Wales, Australia.

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.
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http://dx.doi.org/10.1111/ans.13441DOI Listing
December 2016

High melphalan exposure is associated with improved overall survival in myeloma patients receiving high dose melphalan and autologous transplantation.

Br J Clin Pharmacol 2016 07 27;82(1):149-59. Epub 2016 Apr 27.

The Children's Hospital at Westmead, Hawkesbury Rd, Westmead, 2145.

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.
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http://dx.doi.org/10.1111/bcp.12906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917807PMC
July 2016

Second Cancer Risk and Late Mortality in Adult Australians Receiving Allogeneic Hematopoietic Stem Cell Transplantation: A Population-Based Cohort Study.

Biol Blood Marrow Transplant 2016 May 6;22(5):949-56. Epub 2016 Feb 6.

Research Portfolio, The University of Sydney, Sydney, Australia.

We quantified the risk of second cancer and late mortality in a population-based Australian cohort of 3273 adult (≥15 years) allogeneic hematopoietic stem cell transplant recipients (1992 to 2007). Most recipients received nonradiation-based conditioning and a peripheral blood graft from a matched related donor. Using record linkage with death and cancer registries, 79 second cancers were identified a median of 3.5 years after transplantation. The competing-risk adjusted cumulative incidence of second cancers was 3.35% (95% CI, 2.59 to 4.24) at 10 years, and the cancer risk relative to the matched general population was 2.10 (95% CI, 1.65 to 2.56). We observed an excess risk of melanoma and lip, tongue, esophagus, and soft tissue cancers. Cancer risk relative to the general population was elevated for those transplanted for lymphoma, some leukemia subtypes, and severe aplastic anemia, recipients who developed chronic graft-versus-host disease (cGVHD) and irrespective of radiation-based conditioning or stem cell source. In those alive 2 years after transplantation (n = 1463), the cumulative incidence of late mortality was 22.2% (95% CI, 19.7 to 24.9) at 10 years, and the risk of death relative to the matched general population was 13.8 (95% CI, 12.2 to 15.6). In multivariable modeling, risk of late death was reduced for females compared with males and those transplanted for chronic myeloid leukemia compared with acute myeloid leukemia; risk was increased for recipients with discordant sex donors, cGVHD, those undergoing second transplants, and disease relapse. Adults undergoing allogeneic transplantation have unique cancer and mortality risk profiles that continue to warrant prevention and surveillance activities targeted at high-risk subgroups.
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http://dx.doi.org/10.1016/j.bbmt.2016.01.027DOI Listing
May 2016

A Review of Hematopoietic Cell Transplantation in Australia and New Zealand, 2005 to 2013.

Biol Blood Marrow Transplant 2016 Feb 16;22(2):284-291. Epub 2015 Sep 16.

Department of Haematology and BMT, Royal Melbourne Hospital, Parkville, Victoria, Australia.

This report describes hematopoietic cell transplantation (HCT) activity and outcome in Australia and New Zealand during the years 2005 to 2013. In 2013, 1018 autologous, 221 allogeneic with related donors, and 264 allogeneic with unrelated donors HCT were performed in 40 centers in Australia, with corresponding figures of 147, 39, and 47 in 6 centers in New Zealand. Annual numbers of HCT in 2013 increased, compared to 2005, by 25% in Australia and by 52% in New Zealand. The majority of both allogeneic and autologous HCT used peripheral blood as the stem cell source for all years studied. Major indications for transplantation were acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), plasma cell disorders, and non-Hodgkin lymphoma (NHL). Overall survival probabilities at 5 years after transplantation for adult (16+) allogeneic first HCT recipients were 54.2% for ALL, 46.0% for AML, 48.4% for myelodysplastic syndromes, and 58.6% for NHL. Consistent patterns over time include a steady increase in HCT, particularly for older recipients, relatively constant numbers of allografts using cord blood, and a recent increase in the number of allografts with 2 or more HLA-mismatched related donors.
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http://dx.doi.org/10.1016/j.bbmt.2015.09.009DOI Listing
February 2016

Post-transplant lymphoproliferative disease in heart and lung transplantation: Defining risk and prognostic factors.

J Heart Lung Transplant 2015 Nov 11;34(11):1406-14. Epub 2015 Jun 11.

Department of Haematology, St Vincent's Hospital, Sydney, New South Wales, Australia. Electronic address:

Background: 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.

Methods: 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.

Results: 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%.

Conclusion: 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.
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http://dx.doi.org/10.1016/j.healun.2015.05.021DOI Listing
November 2015

A population-based cohort study of late mortality in adult autologous hematopoietic stem cell transplant recipients in Australia.

Biol Blood Marrow Transplant 2014 Jul 13;20(7):937-45. Epub 2014 Mar 13.

Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.

We assessed overall and cause-specific mortality and risk factors for late mortality in a nation-wide population-based cohort of 4547 adult cancer patients who survived 2 or more years after receiving an autologous hematopoietic stem cell transplantation (HSCT) in Australia between 1992 and 2005. Deaths after HSCT were identified from the Australasian Bone Marrow Transplant Recipient Registry and through data linkage with the National Death Index. Overall, the survival probability was 56% at 10 years from HSCT, ranging from 34% for patients with multiple myeloma to 90% for patients with testicular cancer. Mortality rates moved closer to rates observed in the age- and sex-matched Australian general population over time but remained significantly increased 11 or more years from HSCT (standardized mortality ratio, 5.9). Although the proportion of deaths from nonrelapse causes increased over time, relapse remained the most frequent cause of death for all diagnoses, 10 or more years after autologous HSCT. Our findings show that prevention of disease recurrence remains 1 of the greatest challenges for autologous HSCT recipients, while the increasing rates of nonrelapse deaths due to the emergence of second cancers, circulatory diseases, and respiratory diseases highlight the long-term health issues faced by adult survivors of autologous HSCT.
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http://dx.doi.org/10.1016/j.bbmt.2014.03.006DOI Listing
July 2014

A population-based analysis of the effect of autologous hematopoietic cell transplant in the treatment of multiple myeloma.

Leuk Lymphoma 2013 Aug 28;54(8):1671-6. Epub 2013 Jan 28.

Australasian Bone Marrow Transplant Recipient Registry (ABMTRR), Darlinghurst, NSW, Australia.

This population registry-based study followed all cases of myeloma diagnosed in New South Wales, Australia, during 2002-2005 and compared survival outcomes of those who proceeded to autologous hematopoietic cell transplant (HCT) with those who did not. Data available consisted of demographic details and survival, and did not include disease details or treatment type or response. Of 708 patients, 270 (38%) had a HCT. The 5-year overall survival (OS) of HCT recipients was significantly better than for those who did not proceed to HCT (62% vs. 54%, p = 0.003). HCT was a significant favorable risk factor for OS, while age over 60 was an adverse risk factor. However, for patients alive at 1 year from diagnosis, there was no significant difference in survival between HCT and non-HCT patients, suggesting that worse disease biology and/or coexisting morbidities were likely to be major reasons for the poorer outcome for non-HCT patients.
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http://dx.doi.org/10.3109/10428194.2013.763396DOI Listing
August 2013

Outcomes of hematopoietic stem cell transplantation in primary immunodeficiency: a report from the Australian and New Zealand Children's Haematology Oncology Group and the Australasian Bone Marrow Transplant Recipient Registry.

Biol Blood Marrow Transplant 2013 Mar 7;19(3):338-43. Epub 2012 Dec 7.

Centre for Children's Cancer and Blood Disorders, Sydney Children's Hospital, Randwick, NSW, Australia.

We performed a retrospective analysis on the outcomes of 135 hematopoietic stem cell transplantations (HSCTs) for primary immunodeficiency disorders in Australian and New Zealand Children's Haematology Oncology Group transplantation centers between 1992 and 2008. The most common indications for HSCT were severe combined immunodeficiency, Wiskott-Aldrich syndrome, and chronic granulomatous disease. Five-year overall survival (OS) was 72% for the entire cohort. Disease-specific 5-year OS was 70% for severe combined immunodeficiency, 81% for Wiskott-Aldrich syndrome, and 69% for chronic granulomatous disease. Transplantation-related mortality (TRM) was 10% at day +100. TRM and OS were equivalent in recipients of related and unrelated donor transplants. Source of stem cells had no impact on TRM or OS with outcomes following unrelated umbilical cord blood similar to unrelated bone marrow. The presence of interstitial pneumonitis, active cytomegalovirus infection, or veno-occlusive disease were all independent variables that significantly decreased OS. This large series supports the use of HSCT as curative therapy for a range of primary immunodeficiency disorders, demonstrating excellent survival after both related and unrelated donor transplantation.
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http://dx.doi.org/10.1016/j.bbmt.2012.11.619DOI Listing
March 2013

Allogeneic hematopoietic cell transplant for multiple myeloma using reduced intensity conditioning therapy, 1998-2006: factors associated with improved survival outcome.

Leuk Lymphoma 2011 Sep;52(9):1727-35

Australasian Bone Marrow Transplant Recipient Registry, Darlinghurst, NSW, Australia.

This study reports on the outcome of 95 allogeneic hematopoietic cell transplants (HCTs) using reduced intensity conditioning (RIC) performed for patients with multiple myeloma (MM) in Australia and New Zealand between 1998 and 2006. The median age at HCT was 52 years. Of the 32 patients for whom the allograft was performed as a first transplant, 15 (47%) had their allograft less than 1 year from diagnosis, while for the 63 patients who had an allograft following an autograft, nine (14%) were allografted within 1 year post-diagnosis (p < 0.001). The cumulative incidence of transplant-related mortality (TRM) was 19% at 1 year post-transplant. At 5 years post-transplant the overall survival (OS) was 40% and progression-free survival (PFS) was 23%, with no apparent survival plateau. Three factors were independently favorable predictors of OS in a Cox regression model: immunoglobulin G (IgG) myeloma (hazard ratio [HR] = 0.42, 95% confidence interval [CI] 0.24-0.75, p = 0.004), a human leukocyte antigen (HLA)-identical sibling donor (HR = 0.37, 95% CI 0.18-0.74, p = 0.005), and less than 1 year between MM diagnosis and RIC HCT (HR = 0.27, 95% CI 0.12-0.59, p = 0.001). Patterns of outcome indicate that RIC HCT may offer the potential for cure for only a small group of patients with MM.
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http://dx.doi.org/10.3109/10428194.2011.582201DOI Listing
September 2011

Allogeneic hematopoietic cell transplantation for chronic myelofibrosis in Australia and New Zealand: older recipients receiving myeloablative conditioning at increased mortality risk.

Biol Blood Marrow Transplant 2012 Feb 11;18(2):302-8. Epub 2011 May 11.

Australasian Bone Marrow Transplant Registry, 20 Leichhardt St., Darlinghurst, NSW 2010, Australia.

This retrospective registry analysis examined predictive factors for outcome in 57 patients who underwent allogeneic or syngeneic hematopoietic cell transplantation (HCT) for chronic myelofibrosis (CM), either primary (n = 49) or following an antecedent condition (n = 8), reported to the Australasian Bone Marrow Transplant Registry (ABMTRR) between 1993 and 2005. During the 6 years 2000 to 2005, 40 HCTs were performed for CM compared with 17 in the 7 years 1993 to 1999. Twenty-four recipients (42%) were age 50 or over at transplantation; all of these patients were transplanted after 1997, and 15 were given reduced intensity conditioning (RIC) pretransplantation. The cumulative incidence of transplantation-related mortality was 18% at 100 days and 25% at 1 year posttransplantation. Up to 1 year posttransplantation 16 patients died, with the most common causes being infection (n = 6) and graft-versus-host disease (GVHD) (n = 5). A total of 27 patients survived for 3 years or longer posttransplantation. None of these patients required regular red blood cell transfusions, and of the 17 who had not had splenectomies, none had detectable splenomegaly. Twelve patients had no detectable bone marrow fibrosis, 7 had grade 1 fibrosis, and in 8 patients no information was available. The overall survival (OS) probability for all patients was 72% at 1 year and 58% at 5 years posttransplantation. Patients age 50 and over who received myeloablative conditioning fared poorly, with 1-year overall actuarial survival of 44% compared with 77% for all other patients (P = .007). In multivariate analysis, age 50 years and over at transplantation was the only significant independent unfavorable risk factor for survival post-HCT (hazard ratio 2.71, 95% confidence interval 1.16-6.34, P = .02). This study shows a clear increase in annual numbers of allogeneic HCT performed for CM in Australia and New Zealand in recent years. Five-year survival was favorable compared with international studies, but for older recipients who received myeloablative conditioning, mortality risk was elevated.
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http://dx.doi.org/10.1016/j.bbmt.2011.05.003DOI Listing
February 2012

Incidence and reasons for late failure after allogeneic haematopoietic cell transplantation following BuCy2 in acute myeloid leukaemia.

Br J Haematol 2010 Feb 11;148(4):623-6. Epub 2009 Oct 11.

Division of Haematology/Oncology, The Ohio State University, Columbus, OH, USA.

The long-term follow-up is presented for 317 patients with acute myeloid leukaemia who underwent human leucocyte antigen-identical sibling marrow transplants between 1984 and 1995 following preparation with busulfan 16 mg/kg and cyclophosphamide 120 mg/kg. Among the 142 (45%) who were alive and leukaemia-free 3 years following transplantation, the leukaemia-free survival at 15 years was 72.8%. The cumulative incidence of late (>3 years beyond transplant) non-relapse mortality at 15 years was 12.9% and of late relapse was 16.5%. None of the variables considered (including age, disease stage, and graft-versus-host disease) were predictive of late failure.
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http://dx.doi.org/10.1111/j.1365-2141.2009.07947.xDOI Listing
February 2010

Relative survival of long-term hematopoietic cell transplant recipients approaches general population rates.

Biol Blood Marrow Transplant 2009 Oct 3;15(10):1323-30. Epub 2009 Aug 3.

ABMTRR, Darlinghurst NSW, Australia.

Whether the annual mortality rates of long-term hematopoietic cell transplant (HCT) survivors ever return to that of the general population is unclear. This study sought to determine the annual long-term mortality rates of allogeneic and autologous HCT recipients who had survived 5 years or more disease-free posttransplant and calculate their relative survival rates. Patients were included if they had a first allogeneic or syngeneic HCT for acute leukemia, chronic myelogenous leukemia (CML) or myelodysplastic syndromes (MDS), or autologous HCT for acute myelogenous leukemia (AML) or lymphoma in Australia or New Zealand between 1992 and 2001, recorded on the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) database, and were known to have survived, disease free, 5 years or more posttransplant. The annual mortality rates of 5-year transplant survivors were compared to standard Australian and New Zealand populations using relative survival. A total of 1461 HCT survivors (688 postallograft, 773 postautograft) were included in this study. The 10-year survival probability for 5-year allograft survivors was slightly higher than that of 5-year autologous survivors (93.4% versus 89.6%, P=.06). The relative survival of both allogeneic and autologous 5-year survivors was never <97% of that of the general population. However, it was statistically significantly lower than expected in the sixth to ninth years posttransplant, with no obvious pattern of either improvement or deterioration from 6 to 10 years posttransplant. This study indicates that annual relative survival rates of long-term survivors of allogeneic HCT performed in Australia and New Zealand for acute lymophoblastic leukemkia (ALL), AML, CML, and MDS are slightly, but significantly lower than population rates in the 6th to 10th years posttransplant. Annual relative survival rates of long-term survivors of autologous HCT performed in Australia and New Zealand for AML and lymphomas are also slightly lower than population rates up to the 10th year posttransplant. Late deaths from transplant and disease-related causes are unusual, but continue to occur for many years post-HCT.
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http://dx.doi.org/10.1016/j.bbmt.2009.06.014DOI Listing
October 2009

Late mortality and relapse following BuCy2 and HLA-identical sibling marrow transplantation for chronic myelogenous leukemia.

Biol Blood Marrow Transplant 2009 Jul;15(7):851-5

Department of Hematologic Oncology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only known curative therapy for chronic myelogenous leukemia (CML). Failure, because of relapse or nonrelapse mortality (NRM), generally occurs within 3 years of transplantation, but large studies with long-term follow-up are limited. We present mature results in 335 patients with CML who underwent allogeneic bone marrow transplantation (BMT) from HLA-identical siblings following busulfan and cyclophosphamide (BU/Cy2). Two hundred twenty-nine were in chronic phase (CP) and 106 in accelerated or blastic phase at transplantation. Median follow-up exceeded 14 years. The estimated probability of 18-year leukemia-free survival (LFS) for CP patients was 55.6% and for those beyond CP, 10.5%. Of 182 patients who survived leukemia-free at 3 years, the estimated probability of LFS at 18 years was 61.9%. Late relapse (P = .039) and late NRM (P = .008) occurred at higher rates in patients beyond CP at transplantation. There was no plateau in LFS.
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http://dx.doi.org/10.1016/j.bbmt.2009.03.013DOI Listing
July 2009

Human gastrointestinal neoplasia-associated myofibroblasts can develop from bone marrow-derived cells following allogeneic stem cell transplantation.

Stem Cells 2009 Jun;27(6):1463-8

Royal Brisbane and Women's Hospital Foundation Clinical Research Centre, Queensland Institute of Medical Research, Brisbane, Australia.

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.
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http://dx.doi.org/10.1002/stem.63DOI Listing
June 2009

Haemopoietic stem cell transplantation for children in Australia and New Zealand, 1998-2006: a report on behalf of the Australasian Bone Marrow Transplant Recipient Registry and the Australian and New Zealand Children's Haematology Oncology Group.

Med J Aust 2009 Feb;190(3):121-5

Oncology/Haematology Service, Royal Children's Hospital, Brisbane, QLD.

Objective: To document haemopoietic stem cell transplantation (HSCT) activity and trends among paediatric patients in Australia and New Zealand.

Design, Setting And Participants: A retrospective analysis of data reported to the Australasian Bone Marrow Transplant Recipient Registry by the seven paediatric HSCT institutions in Australia and New Zealand over the 9-year period 1998-2006, with particular focus on the most recent years (2002-2006).

Main Outcome Measures: Types of HSCT performed; transplant-related mortality (TRM); stem cell sources; indications for HSCT; causes of death after HSCT.

Results: Over the period 1998-2006, 522 autologous HSCT procedures (41%) and 737 allogeneic procedures (59%) were performed. About 60% of allogeneic transplants involved alternative donors (donors other than a human leukocyte antigen-matched sibling). The use of umbilical cord blood as a source of haemopoietic stem cells has doubled since 1998, with 34% of allogeneic transplants in 2006 using cord blood. Over the period 2002-2006, the median age of patients receiving transplants was 7 years (range, 0-19 years). The most common indications for allogeneic HSCT were acute lymphoblastic leukaemia (33%) and acute myeloid leukaemia (24%). The most common indications for autologous HSCT were neuroblastoma (23%), medulloblastoma (21%) and Ewing sarcoma (10%). TRM at 1 year after transplant was 22% for alternative donor transplants, 7% for matched-sibling transplants and 5% for autologous transplants. Relapse or persistence of a child's underlying condition accounted for 54% of all deaths within 1 year after transplant.

Conclusions: HSCT is an important procedure for children with a range of life-threatening illnesses. Local trends in the indications for HSCT, donor selection and TRM reflect contemporary international practice.
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http://dx.doi.org/10.5694/j.1326-5377.2009.tb02309.xDOI Listing
February 2009

Hematopoietic stem cell transplantation in Australia and New Zealand, 1992-2004.

Biol Blood Marrow Transplant 2007 Aug 23;13(8):905-12. Epub 2007 May 23.

ABMTRR, Darlinghurst, NSW Australia.

The Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) commenced collecting data on hematopoietic stem cell transplantation (HSCT) in 1992, and by 2004 had accrued more than 12,000 transplant records from 44 centers. In 2004 the Australian annual per capita autograft activity rate was almost twice that of New Zealand (381 per 10 million compared to 195), whereas the 2 countries had similar allografting activity rates (Australia 145, New Zealand 133). The annual rates of allogeneic HSCT per 10 million population in Australia and New Zealand in 2004 were similar to those in European countries of comparable socioeconomic status. Among the most prominent trends between 1998 and 2004 were increases in the numbers of allogeneic HSCT using peripheral blood stem cells (PBSC), the emergence of reduced intensity conditioning in allogeneic HSCT, increases in numbers of autologous HSCT for recipients aged 60 and over, increases in allogeneic HSCT with unrelated donors, and decreases in numbers of allogeneic HSCT for chronic myelogenous leukemia and autologous HSCT for breast cancer. The cumulative incidence of transplant-related mortality (TRM) at 100 days posttransplant progressively fell over the years 1992 to 2003 and was 8.1% for allogeneic HSCT and 1.1% for autologous HSCT in 2003. The ABMTRR is a valuable data resource providing timely and accurate information on HSCT activity in Australia and New Zealand. Full enumeration of HSCT activity in the 2 countries by the ABMTRR enhances its value in clinical planning and management.
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http://dx.doi.org/10.1016/j.bbmt.2007.04.003DOI Listing
August 2007

Equivalent survival for sibling and unrelated donor allogeneic stem cell transplantation for acute myelogenous leukemia.

Biol Blood Marrow Transplant 2007 May 23;13(5):601-7. Epub 2007 Mar 23.

Haematology Department, St. Vincent's Hospital, Darlinghurst, NSW, Australia.

Recent studies have shown comparable survival outcomes for unrelated donor (URD) stem cell transplantation in chronic myelogenous leukemia compared to sibling donors. We compared outcomes for 105 patients aged 16 to 59 years undergoing URD transplants for acute myelogenous leukemia (AML) who were reported to the Australasian Bone Marrow Transplant Recipient Registry between 1992 and 2002, and a strictly selected matching set of 105 HLA-matched sibling donor (MSD) transplants. There was no significant difference between URD and MSD controls in the distributions of time from diagnosis to transplant, donor-recipient sex match, prior therapies, donor age, or performance status. The median follow-up of live URD patients was 4.4 years and for live MSD controls was 6.3 years. There were 18 good risk (complete remission [CR]1) and 87 poor risk (>CR1) recipients in both URD and sibling groups. Five-year disease-free survival (DFS) was not significantly different for good-risk URD and sibling donor recipients (62% versus 40%, P = .2), or poor-risk URD and sibling recipients (21% versus 25%, P = .2). In a stratified multivariate Cox regression model, the independent adverse risk factors for DFS were recipient cytomegalovirus positivity (P = .01) and the interaction of URD and earlier year of transplant (P = .006). Both neutrophil and platelet engraftment were significantly more rapid in the sibling group, but transplant-related mortality at 100 days was not significantly different. There was no difference in the cumulative incidence of acute graft-versus-host disease grade II or above at 100 days. Relapse occurred in 28% of good risk URD subjects and 16% of siblings (P = .3), and in poor risk subjects 39% and 29%, respectively (P = .2). Based on this data, URD allografts should be considered in AML patients without a matched sibling donor. This study provides a rationale for a larger prospective study of risk factors in allogeneic transplantation for AML and a guide on the subset of patients who may most benefit from an unrelated donor allograft in AML.
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http://dx.doi.org/10.1016/j.bbmt.2007.01.073DOI Listing
May 2007