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Evaluation of Second Solid Cancers After Hematopoietic Stem Cell Transplantation in European Patients.
Tichelli A et al. JAMA Oncol. 2018 Nov 21

This is an important study by the Transplant Complications WP focusing on the clinical outcome of secondary solid cancers (SSCs) that occur after HCT. Up until now, the literature on this field provided good documentation of the incidence and risk factors of SSCs after HCT, but hardly any evidence on the outcomes of these patients. Here, the TCWP uses data on a large population of 4065 HCT recipients with multiple forms of SSCs to describe not only the 5-year survival rates for multiple types of SCCs, but most importantly, to identify types of SSCs, such as bladder, breast, colorectal, endometrial, kidney, melanoma and prostate, in which the standardized mortality ratio is higher than in patients with the novo solid cancers. These data are critical to inform and counsel patients who develop SSCs after HCT and set the ground for further investigation on specific therapeutic strategies for these patients.

The eGVHD App has the potential to improve the accuracy of graft-versus-host disease assessment: a multicenter randomized controlled trial.
Schoemans HM et al. Haematologica. 2018 Oct.

The diagnosis and staging of acute and chronic GVHD has been shown to be challenging for healthcare professionals. This led to the development of the eGVHD App in collaboration between the University of Leuven, the EBMT Transplant Complications WP and the NIH. In the past few years, the eGVHD App was initially developed and presented as a proof of concept, then assessed in real-life by professionals at EBMT educational events, and finally made available freely on our website as an educational tool for healthcare professionals who face the challenging assessment of patients with GVHD. In this new study, the team led by Dr. Schoemans takes an additional step forward to formally evaluate in a randomized controlled trial the accuracy of the eGVHD App compared to traditional assessment methods. The results of the trial show that the use of the GVHD App increases over 6-fold the probability of assessing GVHD correctly, both for diagnosis and severity scoring. This benefit of using the App applied to both acute and chronic GVHD and led to a significantly increased inter-observer agreement compared to standard practice. Beyond its value as an educational tool, this new study provides evidence that eGVHD App-assisted assessment of GVHD is more accurate than current standard practice and has the potential to improve the quality of outcome data registration in allogeneic stem cell transplantation.

High-risk chronic lymphocytic leukemia in the era of pathway inhibitors: integrating molecular and cellular therapies.
Dreger P et al. Blood. 2018 Aug 30

The treatment paradigm for high-risk chronic lymphocytic leukemia (CLL) is changing in recent years with the arrival of pathway inhibitors (PIs), such as kinase inhibitors and BCL2 antagonists. These drugs have improved dramatically the outcome of patients with clinical and/or genetic resistance to conventional chemoimmunotherapy (CIT). In this changing context, the role of cellular therapies, including allogeneic HCT and novel CAR-T cells, should be re-evaluated. A group of international experts on behalf of the European Research Initiative on CLL and the EBMT proposes this clinically relevant revision of the concept of high-risk CIT-resistant CLL. Patients with clinically CIT-resistant CLL with TP53 aberrations, but fully responsive to PI (high-risk-I type) are largely the domain of PI-based therapy, and therefore, cellular therapies (ie, allogeneic HCT) remain an option only in selected patients of this group with low individual HCT-related risk. On the other hand, patients with CLL resistant to both CIT and PI (high-risk-II type), for whom pharmacological treatment options are exhausted, should be considered for cellular therapies. This revision of the concept of high-risk CLL patients driven by TP53 and response to PI informs the sequence of use and potential synergistic effect of molecular and cellular therapies, which are not mutually exclusive, to exploit their full potential in high-risk CIT-resistant patients with CLL.

European guidelines for primary antifungal prophylaxis in adult haematology patients: summary of the updated recommendations from the European Conference on Infections in Leukaemia.
Maertens JA et al. J Antimicrob Chemother. 2018 Dec 1

The European Conference on Infections in Leukaemia (ECIL) has recently updated its guidelines on antifungal prophylaxis using the grading system of IDSA. For recipients of allogeneic HCT, the guidelines now have been revised to differentiate cases with low risk of mould infection during the pre-engraftment phase, for whom fluconazole is still the recommended options, from patients with high-risk of mould infection, for whom the recommendation is strongly against the use of a mould-inactive azole such as fluconazole. In these patients, posazonazole is strongly recommended for preventing invasive mould disease in patients with GVHD, but in patients with high-risk of mould infection during the pre-engraftment phase the evidence to recommend a particular azole for antifungal prophylaxis is less strong. Posaconazole remains the drug of choice for patients undergoing remission-induction chemotherapy for AML and myelodysplastic syndrome (MDS), although some centers with lower incidence of invasive mould disease can still use other strategies as part of an integrated care strategy that includes screening with biomarkers and imaging. The guidelines have also extended the analyses to provide recommendations for other hematological diseases besides AML and allogeneic HCT. However, the need for primary prophylaxis such patient groups was less clear and should be defined by the estimated risk of invasive fungal disease (IFD).

Haploidentical versus unrelated allogeneic stem cell transplantation for relapsed/refractory acute myeloid leukemia: A report of 1578 patients from the Acute Leukemia Working Party of EBMT.
Brissot E et al. Haematologica. 2018 Oct 25

Allogeneic HCT is the only therapeutic option that offers prolonged survival and cure for patients with primary refractory or relapsed acute myeloid leukemia. In the absence of a matched sibling donor, transplantation from unrelated 10/10 or 9/10 and haploidentical donors are potential alternatives. This retrospective study from the Acute Leukemia WP compares the outcomes of allogeneic HCT in this setting using unrelated donors (10/10, n=1111 or 9/10, n=383) to those using haploidentical donors with post-transplant cyclophosphamide (n=199). In multivariate analysis, there was no significant difference in leukemia-free survival, overall survival, relapse incidence, non-relapse mortality, neither graft-versus-host-disease-free relapse-free survival between the 3 groups. Two predictive factors were associated with a higher relapse incidence: first or second relapse compared to primary refractory acute myeloid leukemia and poor cytogenetics. Overall, this important study shows that allogeneic HCT may rescue about 25 % of AML patients with active disease, and suggests that the outcomes of transplants from haploidentical donor were comparable to those from 10/10 and 9/10 unrelated donor, and thus, are a valid option for AML patients with active disease.

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