Leukemia Research 38 (2014) 176–179 Contents lists available at ScienceDirect Leukemia Research journa l h o me pag e: www.elsevier.com/locate/leukres The role of hematopoietic cell transplantation in adult ALL: Clinical equipoise persists K. Paulson a,b,* , D. Szwajcer a,b , C.B. Raymond c , M.D. Seftel d a Section of Haematology/Oncology, Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada b CancerCare Manitoba, Winnipeg, MB, Canada c Manitoba Centre for Health Policy, University of Manitoba, Winnipeg, MB, Canada d Division of Medical Oncology&Hematology, Department of Medicine, University of Toronto, Toronto, ON, Canada a r t i c l e i n f o Article history: Received 31 July 2013 Received in revised form 21 October 2013 Accepted 23 October 2013 Available online 1 November 2013 Keywords: Acute lymphoblastic leukemia Hematopoietic stem cell transplant Evidence based medicine a b s t r a c t Adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1) may be treated either with ongoing systemic chemotherapy or with allogeneic hematopoietic cell transplantation (alloHCT). Despite the presence of phase III trials to support clinical decision-making, we hypothesized that physi- cians who treat adult ALL would demonstrate wide practice variation. Canadian hematologists who treat ALL were surveyed electronically. Overall, 69 of 173 physicians responded (40%). There was high agreement with offering alloHCT for ALL with high-risk cytogenetics or induction failure after a single chemotherapy cycle. However, only a minority of respondents felt that age >35 years was an indication for alloHCT in CR1. Almost all respondents (96%) felt that a well-matched unrelated donor was an accept- able alternative to a sibling donor. There was uncertainty about the role of cord blood (53% agree) and the utility of reduced intensity conditioning HCT (41% agree). In contrast to the results of the MRC/ECOG study, respondents considered alloHCT to be particularly helpful in high-risk patients. Consensus was lacking on the use of cord blood, RIC alloHCT, and the application of MRD. Equipoise exists on the role of alloHCT in CR1 in ALL, suggesting that further trials in this area are required. © 2013 Elsevier Ltd. All rights reserved. 1. Introduction The practice of evidence-based medicine faces many challenges in hematopoietic cell transplantation (HCT). Prospective random- ized trials are rare, and lesser levels of evidence such as cohort studies and case series often guide clinical decision-making. In addition, HCT is a rapidly evolving field, and new techniques are often adopted into clinical practice before the availability of pub- lished clinical trials. The aim of this study was to understand how HCT clinicians integrate the available evidence to make practi- cal decisions in the management of acute lymphoblastic leukemia (ALL). We chose ALL as a sentinel disease to study for several rea- sons. One large prospective trial was published in 2008, which produced results that challenged conventional clinical practice and prompted the publication of meta-analyses [1,2]. In addition, the use of new strategies such as reduced intensity conditioning (RIC) HCT, cord blood transplantation, and measurement of minimal residual disease (MRD) have been adopted without the availability * Corresponding author at: ON2050, CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB, Canada. Tel.: +1 204 771 7238; fax: +1 204 786 0196. E-mail addresses: Kristjan.paulson@cancercare.mb.ca, kpaulson@cancercare.mb.ca (K. Paulson). of high grade evidence to support their use. We sought to under- stand how clinicians practiced evidence-informed decision making in ALL, integrating the results of one large clinical trial into clinical practice. The optimal management of acute lymphoblastic leukemia (ALL) in adults requires initial remission induction chemother- apy accompanied by careful patient selection for allogeneic hematopoietic cell transplantation (AlloHCT). However, pediatric- like chemotherapy protocols are being adopted, with the hope that they might improve the complete response rate and overall survival and, for some patients, avoid the need for alloHCT in CR1 [3,4]. In addition, the field of HCT has been revolutionized over the last two decades, with widespread use of unrelated donors, the advent of RIC HCT, and dramatic reductions in treatment related mortality [5]. The pivotal MRC/ECOG study found a dramatically lower relapse rate among patients assigned to receive allogeneic HCT as com- pared to maintenance chemotherapy [1]. However, the lower relapse rate in allogeneic HCT was balanced by increased therapy- related toxicity. In subgroup analysis, the benefit with HCT was isolated to standard risk patients, but not in high risk ones. This observation is contrary to clinical practice in most other hemato- logic malignancies, in which benefits with HCT are primarily seen in high-risk patients [6]. Survival after first relapse of ALL remains 0145-2126/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.leukres.2013.10.021