Publications by authors named "Duncan Purtill"

24 Publications

  • Page 1 of 1

Gastric Band Infection Complicated by Immune Reconstitution Inflammatory Syndrome and Cured in the Context of Allogeneic Hematopoietic Stem Cell Transplantation.

Open Forum Infect Dis 2021 Feb 23;8(2):ofaa637. Epub 2020 Dec 23.

Department of Infectious Diseases, Fiona Stanley Hospital, Perth, Australia.

We present a case of abdominal gastric band-associated infection, manifesting after the onset of acute myeloid leukemia, complicated by immune reconstitution inflammatory syndrome (IRIS), and cured while receiving an allogeneic hematopoietic stem cell transplant. IRIS should be considered in less classical situations where there is unexplained clinical deterioration.
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http://dx.doi.org/10.1093/ofid/ofaa637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849998PMC
February 2021

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

Variable CD34+ recovery of cryopreserved allogeneic HPC products: transplant implications during the COVID-19 pandemic.

Blood Adv 2020 09;4(17):4147-4150

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

Donor registries and transplantation societies recommend cryopreservation of unrelated donor hemopoietic progenitor cell (HPC) products before the recipient commences conditioning therapy to mitigate the donor and travel risks associated with the COVID-19 pandemic. However, little is known regarding the postthaw quality of such allogeneic products or the effect of precryopreservation storage and processing on these characteristics. We investigated the postthaw CD34+ cell recovery and viability of 305 allogeneic HPC products cryopreserved at 9 laboratories across Australia. Median postthaw CD34+ cell recovery was 76% and ranged from 6% to 122%. Longer transit time before cryopreservation, white cell count (WCC) during storage, and complex product manipulation before cryopreservation were independently associated with inferior postthaw CD34+ cell recovery. Longer precryopreservation transit time and WCC were also associated with inferior postthaw CD34+ cell viability. We conclude that although postthaw CD34+ cell recovery and viability of cryopreserved allogeneic HPC is generally acceptable, there is a significant risk of poor postthaw product quality, associated with prolonged storage time, higher WCC, and complex product manipulation precryopreservation. Awareness of expected postthaw recovery and practices that influence it will assist collection, processing, and transplant centers in optimizing outcomes for transplant recipients.
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http://dx.doi.org/10.1182/bloodadvances.2020002431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479963PMC
September 2020

Australasian Trends in Allogeneic Stem Cell Transplantation for Myelofibrosis in the Molecular Era: A Retrospective Analysis from the Australasian Bone Marrow Transplant Recipient Registry.

Biol Blood Marrow Transplant 2020 12 27;26(12):2252-2261. Epub 2020 Aug 27.

Department of Haematology and Bone Marrow Transplantation, St Vincent's Hospital, Sydney, Australia; University of New South Wales, Sydney, Australia.

To review the updated trends of national practice and outcomes in transplantation to treat myelofibrosis (MF), we retrospectively evaluated 142 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) for primary (n = 94) or secondary (n = 48) MF at an Australian/New Zealand transplantation center between 2006 and 2017. The median duration of follow-up was 51.8 months (range, 3.1 to 148 months). The median age at allo-HSCT was 56 years (range, 26 to 69 years). Fifty-two percent of the patients had HLA-identical sibling donors, and 45% had matched unrelated donors (UD). Conditioning regimens were predominantly reduced intensity (83%). Before transplantation, 16% of the patients had undergone splenectomy or splenic irradiation, and 38% (n = 54) received JAK inhibitor therapy. JAK2 mutation testing was performed in 66.9% of the patients, whereas other mutations (CALR, MPL, ASXL1, SRSF2, U2AF1Q57, EZH2, and IDH1/2) were rarely tested (1.4% to 8.4%). Only 4.2% of patients had next-generation sequencing mutation analysis. The median time to neutrophil engraftment was 19 days (range, 10 to 43 days), and the median time to platelet engraftment was 27 days (range, 13 to 230 days). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 21.4% at 100 days, and that of extensive chronic GVHD (cGVHD) at 5 years was 18.1%. Overall survival (OS) was 67% at 1 year and 57% at 5 years. GVHD-free, relapse-free survival was 54% at 1 year and 42% at 5 years. The cumulative incidence of nonrelapse mortality (NRM) was 16% at 100 days and 25% at 1 year. In multivariate analysis, age ≥65 years and use of an UD were identified as significant unfavorable risk factors for OS and NRM. Use of an UD increased the incidence of aGVHD, whereas administration of antithymocyte globulin/alemtuzumab lowered the risk of both aGVHD and cGVHD. Pretransplantation splenectomy/splenic irradiation had a positive influence on time to engraftment. There have been no improvements in the outcomes of allo-HSCT for MF in Australasia over the last decade, with a low uptake of molecular genomic technology due to limited access to funding.
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http://dx.doi.org/10.1016/j.bbmt.2020.08.024DOI Listing
December 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

Prognostic factors and the impact of frontline therapy in peripheral T-cell lymphoma: 10 years of 'real-world' experience from Western Australia.

Leuk Lymphoma 2019 12 15;60(14):3417-3425. Epub 2019 Jul 15.

Department of Haematology, Fiona Stanley Hospital, Murdoch, Australia.

We present an analysis of 98 consecutive patients with peripheral T-cell lymphoma (PTCL) treated over a 10-year period within Western Australia. The most common frontline therapies were CHO(E)P (47%), HyperCVAD (21%), and reduced intensity therapy or supportive care alone (19%). Median and 4-year overall survival (OS) for the whole cohort were 1.59 years and 34%. Amongst CHO(E)P and HyperCVAD-treated patients, elevated LDH, advanced stage, IPI >1, and non-ALK + ALCL histology predicted inferior progression-free survival (PFS). Inferior OS was predicted by elevated LDH, age >60, IPI >1, and non-ALK + ALCL histology. Response rates and PFS were not significantly different between patients treated with CHO(E)P or HyperCVAD. OS was longer in the HyperCVAD group, however this was not significant on multivariable analysis and appears to relate to the younger age and more aggressive therapy at relapse in this group. Our data confirmed the prognostic utility of the IPI in patients with PTCL and do not demonstrate a clear benefit of HyperCVAD.
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http://dx.doi.org/10.1080/10428194.2019.1637865DOI Listing
December 2019

A multicenter retrospective comparison of induction chemoimmunotherapy regimens on outcomes in transplant-eligible patients with previously untreated mantle cell lymphoma.

Hematol Oncol 2019 Aug 24;37(3):253-260. Epub 2019 May 24.

Department of Haematology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.

Mantle cell lymphoma (MCL) is an uncommon and typically aggressive form of lymphoma. Although often initially chemosensitive, relapse is common. Several induction and conditioning regimens are used in transplant-eligible patients, and the optimal approach remains unknown. We performed an international, retrospective study of transplant-eligible patients to assess impact of induction chemoimmunotherapy and conditioning regimens on clinical outcomes. We identified 228 patients meeting inclusion criteria. Baseline characteristics were similar among the induction groups except for some variation in age. The type of induction chemoimmunotherapy received did not influence overall response rates (ORRs) (0.43), progression-free survival (PFS) (P > .67), or overall survival (OS) (P > .35) on multivariate analysis (PFS and OS). Delivery of autologous stem cell transplant (ASCT) was associated with favorable PFS and OS (0.01) on univariate analysis only; this benefit was not seen on multivariate analysis-PFS (0.36) and OS (0.21). Compared with busulfan and melphalan (BuMel), the use of the carmustine, etoposide, cytarabine, melphalan (BEAM)-conditioning regimen was associated with inferior PFS (HR = 2.0 [95% CI 1.1-3.6], 0.02) but not OS (HR = 1.1 [95% CI 0.5-2.3], 0.81) on univariate analysis only. Within the limits of a retrospective study and modest power for some comparisons, type of induction therapy did not influence ORR, PFS, or OS for transplant-eligible patients with MCL. International efforts are required to perform randomized clinical trials evaluating chemoimmunotherapy induction regimens.
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http://dx.doi.org/10.1002/hon.2618DOI Listing
August 2019

Acute myeloid leukaemia relapsing after allogeneic haemopoietic stem cell transplantation: prognostic factors and impact of initial therapy of relapse.

Intern Med J 2018 03;48(3):276-285

Department of Clinical Haematology and BMT Service, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Background/aims: We sought to determine factors associated with the overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haemopoietic stem cell transplantation (alloHSCT) and the effect of first salvage therapy and subsequent graft-versus-host disease (GVHD) on OSR.

Methods: Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the log-rank test and proportional hazards modelling, respectively and a prognostic index for OSR was derived from multivariate modelling.

Results: On multivariate analysis, relapse within 6 months (hazard ratio (HR) 2.4, P < 0.001) and grade 3-4 acute GVHD preceding relapse (HR 2.0, P = 0.004), were associated with inferior OSR. Patients with 1-2 factors had inferior OSR compared to those with zero factors (all patients: HR 2.3, P < 0.001, patients given salvage: HR 1.8, P < 0.001). The first salvage therapy used post-relapse was donor cell therapy (DCT) (second alloHSCT or donor lymphocyte infusion) in 75, re-induction chemotherapy (CT) in 103, radiotherapy in 8 and interferon-α in 6. Although re-induction CT death rate was low (2%), survival after CT was inferior to DCT (HR 1.9, P < 0.001). No survival benefit was seen for patients who developed GVHD following salvage therapy (P = 0.405).

Conclusion: Patients with AML who relapse beyond 6 months from alloHSCT without prior grade 3-4 acute GVHD have a better outcome from salvage therapy. Salvage treatments employing DCT as the initial treatment of AML relapse confer a survival advantage over CT.
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http://dx.doi.org/10.1111/imj.13522DOI Listing
March 2018

Killer Cell Immunoglobulin-Like Receptor-Ligand Matching and Outcomes after Unrelated Cord Blood Transplantation in Acute Myeloid Leukemia.

Biol Blood Marrow Transplant 2016 07 16;22(7):1284-1289. Epub 2016 Apr 16.

Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.

The effect of killer cell immunoglobulin-like receptor (KIR)-ligand matching on outcomes after unrelated cord blood (CB) transplantation was studied in 461 patients with acute myeloid leukemia, categorizing KIR ligand for HLA-C groups C1 and C2 and Bw4. Donor-recipient HLA matching considered allele-level matching at HLA-A, -B, -C, and -DRB1. Separate analyses were conducted for 6-7/8 HLA-matched and 3-5/8 HLA-matched transplants because HLA matching confounded KIR-ligand matching (ie, KIR-ligand mismatching was less likely with better HLA matching). All patients received single CB unit and myeloablative conditioning. There were no significant differences in nonrelapse mortality (NRM), relapse, and overall mortality by KIR-ligand match status. However, among recipients of 3-5/8 HLA-matched transplants, NRM (HR, 2.26; P = .008) and overall mortality (HR, 1.78; P = .008) but not relapse were higher with KIR-ligand mismatched (host-versus-graft direction) compared with KIR-ligand matched transplants. These data do not support selecting CB units based on KIR-ligand match status for transplants mismatched at 1 or 2 HLA loci. Although transplants mismatched at 3 or more HLA loci are not recommended, avoiding KIR-ligand mismatching in this setting lowers mortality risks.
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http://dx.doi.org/10.1016/j.bbmt.2016.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915071PMC
July 2016

Robust Vaccine Responses in Adult and Pediatric Cord Blood Transplantation Recipients Treated for Hematologic Malignancies.

Biol Blood Marrow Transplant 2015 Dec 10;21(12):2160-2166. Epub 2015 Aug 10.

Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York. Electronic address:

Because cord blood (CB) lacks memory T and B cells and recent decreases in herd immunity to vaccine-preventable diseases in many developed countries have been documented, vaccine responses in CB transplantation (CBT) survivors are of great interest. We analyzed vaccine responses in double-unit CBT recipients transplanted for hematologic malignancies. In 103 vaccine-eligible patients, graft-versus-host disease (GVHD) most commonly precluded vaccination. Sixty-five patients (63%; engrafting units median HLA-allele match 5/8; range, 2 to 7/8) received protein conjugated vaccines, and 63 patients (median age, 34 years; range, .9 to 64) were evaluated for responses. Median vaccination time was 17 months (range, 7 to 45) post-CBT. GVHD (n = 42) and prior rituximab (n = 13) delayed vaccination. Responses to Prevnar 7 and/or 13 vaccines (serotypes 14, 19F, 23F) were seen in children and adults (60% versus 49%, P = .555). Responses to tetanus, diphtheria, pertussis, Haemophilus influenzae, and polio were observed in children (86% to 100%) and adults (53% to 89%) even if patients had prior GVHD or rituximab. CD4(+)CD45RA(+) and CD19(+) cell recovery significantly influenced tetanus and polio responses. In a smaller cohort responses were seen to measles (65%), mumps (50%), and rubella (100%) vaccines. No vaccine side effects were identified, and all vaccinated patients survived (median follow-up, 57 months). Although GVHD and rituximab can delay vaccination, CBT recipients (including adults and those with prior GVHD) have similar vaccine response rates to adult donor allograft recipients supporting vaccination in CBT recipients.
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http://dx.doi.org/10.1016/j.bbmt.2015.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672874PMC
December 2015

Association between Nondominant Unit Total Nucleated Cell Dose and Engraftment in Myeloablative Double-Unit Cord Blood Transplantation.

Biol Blood Marrow Transplant 2015 Nov 23;21(11):1981-4. Epub 2015 Jul 23.

Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York. Electronic address:

Sustained hematopoiesis after double-unit cord blood transplantation (dCBT) is mediated by 1 unit in nearly all patients. To investigate the associations between nondominant unit characteristics and neutrophil engraftment, we studied 129 consecutive myeloablative dCBT recipients. Ninety-five percent (95% confidence interval, 90 to 98) of patients engrafted. Detection of the nondominant unit 21 to 28 days after dCBT was not associated with improved neutrophil engraftment. In univariate analyses, nondominant unit characteristics (infused total nucleated cell [TNC] and viable CD3(+) cell doses) were significantly associated with speed and success of neutrophil engraftment as were dominant unit characteristics (infused TNC; viable CD34(+), viable CD3(+), and viable CD3-56(+)16(+) cell doses; and post-thaw CD34(+) cell viability). In multivariate analysis, higher infused TNC dose of the nondominant unit was independently associated with improved neutrophil engraftment, even when this unit did not contribute to donor hematopoiesis. In further subgroup analysis, this association was only evident when the infused viable CD34(+) cell dose of the dominant unit was low (<1.20 × 10(5)/kg). These findings suggest nondominant units mediate a dose-dependent facilitation of engraftment in myeloablative dCBT and support continued investigation of dCBT biology and the clinical practice of dCBT in adults in whom low cell dose grafts are common.
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http://dx.doi.org/10.1016/j.bbmt.2015.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604060PMC
November 2015

Dominant unit CD34+ cell dose predicts engraftment after double-unit cord blood transplantation and is influenced by bank practice.

Blood 2014 Nov 2;124(19):2905-12. Epub 2014 Sep 2.

Adult Bone Marrow Transplantation Service, Department of Medicine, Weill Cornell Medical College, New York, NY; and.

We investigated the unit characteristics associated with engraftment after double-unit cord blood (CB) transplantation (dCBT) and whether these could be reliably identified during unit selection. Cumulative incidence of neutrophil engraftment in 129 myeloablative dCBT recipients was 95% (95% confidence interval: 90-98%). When precryopreservation characteristics were analyzed, the dominant unit CD34(+) cell dose was the only characteristic independently associated with engraftment (hazard ratio, 1.43; P = .002). When postthaw characteristics were also included, only dominant unit infused viable CD34(+) cell dose independently predicted engraftment (hazard ratio, 1.95; P < .001). We then examined the determinants of infused viable CD34(+) cell dose (precryopreservation count, postthaw recovery, and postthaw viability) in 402 units thawed at our center. This revealed close correlation between precryopreservation and postthaw CD34(+) cell counts (r(2) = 0.73). Median CD34(+) cell recovery was 101%, although it ranged from 12% to 1480%. Notably, units from non-Netcord Foundation for the Accreditation of Cellular Therapy (Netcord-FACT)-accredited banks were more likely to have low recovery (P < .001). Furthermore, although median postthaw CD34(+) cell viability was 92%, 33 (8%) units had <75% viable CD34(+) cells. Units from non-Netcord-FACT-accredited banks and units with cryovolumes other than 24.5 to 26.0 mL were more likely to have poor postthaw viability. Precryopreservation CD34(+) cell dose and banking practices should be incorporated into CB unit selection.
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http://dx.doi.org/10.1182/blood-2014-03-566216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224191PMC
November 2014

Unravelling the prognostic effect of IKZF1 deletions and IGH@-CRLF2 in adult acute lymphoblastic leukaemia.

Pathology 2013 10;45(6):609-12

*Department of Haematology †PathWest Laboratory Medicine, Royal Perth Hospital, Perth ‡School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA, Australia §Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK.

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http://dx.doi.org/10.1097/PAT.0b013e3283653bd1DOI Listing
October 2013

Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning.

Blood 2013 May 14;121(19):3981-7. Epub 2013 Mar 14.

University Medical Center Utrecht, Pediatric Blood and Marrow Transplantation Program, Utrecht, The Netherlands.

We report transplantation outcomes of 258 children with Hurler syndrome (HS) after a myeloablative conditioning regimen from 1995 to 2007. Median age at transplant was 16.7 months and median follow-up was 57 months. The cumulative incidence of neutrophil recovery at day 60 was 91%, acute graft-versus-host disease (GVHD) (grade II-IV) at day 100 was 25%, and chronic GVHD and 5 years was 16%. Overall survival and event-free survival (EFS) at 5 years were 74% and 63%, respectively. EFS after HLA-matched sibling donor (MSD) and 6/6 matched unrelated cord blood (CB) donor were similar at 81%, 66% after 10/10 HLA-matched unrelated donor (UD), and 68% after 5/6 matched CB donor. EFS was lower after transplantation in 4/6 matched unrelated CB (UCB) (57%; P = .031) and HLA-mismatched UD (41%; P = .007). Full-donor chimerism (P = .039) and normal enzyme levels (P = .007) were higher after CB transplantation (92% and 98%, respectively) compared with the other grafts sources (69% and 59%, respectively). In conclusion, results of allogeneic transplantation for HS are encouraging, with similar EFS rates after MSD, 6/6 matched UCB, 5/6 UCB, and 10/10 matched UD. The use of mismatched UD and 4/6 matched UCB was associated with lower EFS.
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http://dx.doi.org/10.1182/blood-2012-09-455238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836041PMC
May 2013

Effect of HLA-matching recipients to donor noninherited maternal antigens on outcomes after mismatched umbilical cord blood transplantation for hematologic malignancy.

Biol Blood Marrow Transplant 2012 Dec 17;18(12):1890-6. Epub 2012 Jul 17.

Eurocord, Hôpital Saint-Louis, Paris, France.

Transplantation-related mortality (TRM) is high after HLA-mismatched umbilical cord blood (UCB) transplantation (UCBT). In utero, exposure to noninherited maternal antigen (NIMA) is recognized by the fetus, which induces T regulator cells to that haplotype. It is plausible that UCBTs in which recipients are matched to donor NIMAs may alleviate some of the excess mortality associated with this treatment. To explore this concept, we used marginal matched-pair Cox regression analysis to compare outcomes in 48 NIMA-matched UCBTs (ie, the NIMA of the donor UCB unit matched to the patient) and in 116 non-NIMA-matched UCBTs. All patients had a hematologic malignancy and received a single UCB unit. Cases and controls were matched on age, disease, disease status, transplantation-conditioning regimen, HLA match, and infused cell dose. TRM was lower after NIMA-matched UCBTs compared with NIMA-mismatched UCBTs (relative risk, 0.48; P = .05; 18% versus 32% at 5 years posttransplantation). Consequently, overall survival was higher after NIMA-matched UCBT. The 5-year probability of overall survival was 55% after NIMA-matched UCBTs versus 38% after NIMA-mismatched UCBTs (P = .04). When faced with the choice of multiple HLA-mismatched UCB units containing adequate cell doses, selecting an NIMA-matched UCB unit may improve survival after mismatched UCBT.
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http://dx.doi.org/10.1016/j.bbmt.2012.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826155PMC
December 2012

Mesenchymal stromal cell therapy for steroid-refractory acute and chronic graft versus host disease: a phase 1 study.

Int J Hematol 2012 Feb 20;95(2):182-8. Epub 2011 Dec 20.

Cell and Tissue Therapies, Western Australia, Royal Perth Hospital, Wellington St, Perth, 6000, Australia.

Steroid-refractory acute graft versus host disease (AGVHD) and chronic graft versus host disease (CGVHD) after allogeneic haematopoietic stem cell transplantation are major causes of morbidity and mortality. We undertook a phase I trial in patients with steroid-refractory AGVHD and CGVHD utilising bone marrow-derived mesenchymal stromal cells (MSC). Additionally, all refractory patients were treated with etanercept concomitantly. The primary end point was safety, and secondary end points were best response achieved and overall survival. A median of two infusions per patient were administered. The response rate overall for AGVHD was complete in seven, partial in four and no response in one patient. Of the seven patients who achieved a complete response, six are alive. The actuarial survival for the overall group of AGVHD was 55% at 30 months. Two patients with CGVHD achieved complete response with two partial responses and three with no response. The survival for those with AGVHD who achieved a complete response compared with those who did not was significant (p = 0.03). We identified no early or late safety issues in the nineteen patients. In view of the poor outlook for steroid-refractory AGVHD, further trials are warranted of MSC with steroid therapy, at the onset of AGVHD before steroid resistance.
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http://dx.doi.org/10.1007/s12185-011-0989-2DOI Listing
February 2012

Umbilical cord blood transplantation for children with thalassemia and sickle cell disease.

Biol Blood Marrow Transplant 2011 Sep 28;17(9):1375-82. Epub 2011 Jan 28.

Clinical Research Unit, Eurocord office, Hôpital Saint Louis APHP, Paris, France.

We examined the efficacy of unrelated cord blood (CB) transplantation in children with thalassemia (n = 35) and sickle cell disease (n = 16), using data reported to 3 registries. Donor-recipient pairs were matched at HLA-A and -B (antigen level) and DRB1 (allele level) in 7 or HLA mismatched at 1 (n = 18), 2 (n = 25), or 3 loci (n = 1). Transplant conditioning was myeloablative (n = 39) or reduced intensity (n = 12). Neutrophil recovery with donor chimerism was documented in 24 patients; 11 patients developed grade II-IV acute graft-versus-host disease (aGVHD) and 10 patients, chronic GVHD (cGVHD). Overall survival (OS) and disease-free survival (DFS) were 62% and 21% for thalassemia and 94% and 50% for sickle cell disease (SCD), respectively. In multivariate analysis, engraftment rate (hazard ratio [HR] 2.2, P = .05) and DFS (HR 0.4, P = .01) were higher with cell dose >5 × 10(7)/kg. The 2-year probability of DFS was 45% in patients who received grafts with cell dose >5 × 10(7)/kg and 13% with lower cell dose. Primary graft failure was the predominant cause of treatment failure occurring in 20 patients with thalassemia and 7 patients with SCD. Primary graft failure was fatal in 5 patients with thalassemia. These results suggest that only CB units containing an expected infused cell dose >5 × 10(7)/kg should be considered for transplantation for hemoglobinopathy.
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http://dx.doi.org/10.1016/j.bbmt.2011.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395002PMC
September 2011

Is there an impact of killer cell immunoglobulin-like receptors and KIR-ligand incompatibilities on outcomes after unrelated cord blood stem cell transplantation?

Best Pract Res Clin Haematol 2010 Jun;23(2):283-90

Department of Hematology, Leiden University Medical Center, the Netherlands.

Donor killer cell immunoglobulin-like receptor (KIR) ligand incompatibility in the graft-versus-host direction is associated with decreased relapse incidence and improved disease-free survival after haploidentical and human leucocyte antigen (HLA)-mismatched unrelated, haematopoietic stem cell transplantation. However, review of all published studies of allogeneic HLA-matched or mismatched stem cell transplantation shows that the results on the relationship between donor-recipient KIR(-ligand) (in)compatibility and outcomes are highly variable, ranging from highly beneficial to detrimental. Reasons for these differences may include the methodology to determine KIR(-ligand) incompatibility, the disease distribution and the transplant protocol or donor type. Two retrospective studies on the effects of KIR-ligand incompatibility in unrelated cord blood transplantation (UCBT) for haematological malignancies have resulted in conflicting results. The Eurocord study showed a favourable effect of KIR-ligand mismatching on relapse incidence and leukaemia-free survival, whereas the Minneapolis study showed no effect on these end points and a detrimental effect on incidence of graft-versus-host disease (GvHD). In patients with non-malignant disorders, KIR-ligand (in)compatibility between donor and recipient was not associated with outcomes in a recent Eurocord analysis. Therefore, the role of natural killer (NK) cell alloreactivity in UCBT is far from clear. It is too early to use a donor-recipient KIR(-ligand) algorithm for selection of a cord blood donor.
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http://dx.doi.org/10.1016/j.beha.2010.05.005DOI Listing
June 2010

Double cord blood transplantation: extending the use of unrelated umbilical cord blood cells for patients with hematological diseases.

Best Pract Res Clin Haematol 2010 Jun;23(2):223-9

Hôpital Saint Louis, Paris, France.

Unrelated umbilical cord blood (UCB) has been widely used to treat patients lacking a well-matched HLA donor. Cell dose is a critical determinant of outcomes in cord blood transplantation, limiting the use of this strategy for low body weight patients. To overcome this limitation, infusion of two partially HLA-matched cord units was adopted as a new strategy. Since 2005, number of adult patients treated with UCB transplant is increased due to the higher number of cells available using two units and to the feasibility of reduced intensity conditioning regimen, extending successfully this strategy to heavier patients or for those with co-morbidities. Approximately 993 adults with hematological diseases have been transplanted with double UCB graft, and reported to Eurocord registry from 1999 to 2010. This article reviews the state of art and future directions with double umbilical cord blood units as a source of hematopoietic stem cells for transplantation.
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http://dx.doi.org/10.1016/j.beha.2010.07.005DOI Listing
June 2010

Influence of nucleated cell dose on overall survival of unrelated cord blood transplantation for patients with severe acquired aplastic anemia: a study by eurocord and the aplastic anemia working party of the European group for blood and marrow transplantation.

Biol Blood Marrow Transplant 2011 Jan 16;17(1):78-85. Epub 2010 Jun 16.

Bone Marrow Transplant Unit, Saint Louis Hospital, Paris, France.

Information is scarce on outcomes after unrelated cord blood transplantation (UCBT) for patients with severe aplastic anemia (SAA). We retrospectively analyzed 71 patients (median age, 13 years; 28 adults) with SAA (9 with paroxysmal nocturnal hemoglobinuria [PNH]) who received a single-unit (n = 57; 79%) or double-unit UCBT (n = 14; 19%) in 32 centers between 1996 and 2009. A reduced-intensity conditioning regimen was provided in 68% of the patients. The cumulative incidence (CI) of neutrophil recovery was 51% ± 6% at day 60, with significantly better engraftment seen in recipients of higher prefreezing total nucleated cell (TNC) dose (>3.9 10(7)/kg; hazard ratio [HR], 1.5; P = .05). The CI of platelet engraftment at day 180 posttransplantation was 37% ± 7%, that of grade II-IV acute GVHD was 20% ± 5%, and that of chronic GVHD at 3 years was 18% ± 5%. At a median follow-up of 35 months (range, 3-83 months), the estimated probability of 3-year overall survival (OS) was 38% ± 6%. Significantly improved OS was seen in recipients of >3.9 10(7) TNCs/kg prefreezing (45%, compared with 18% for recipients of ≤ 3.9 10(7) TNC/kg; HR, 0.4; P = .007). These results highlight the fundamental role of cell dose for both engraftment and OS in patients with SAA undergoing UCBT.
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http://dx.doi.org/10.1016/j.bbmt.2010.06.011DOI Listing
January 2011