-
1.
Gaining Consensus Around Patient Risk Groups and Prognostic Profiles to Guide CMV Management Among Patients With Allogeneic Hematopoietic Stem Cell Transplant: Insights From a Delphi Panel With Hematopoietic Stem Cell Transplant Experts
Graf, M., Tuly, R., Pednekar, P., Wang, C., Batt, K.
Transplantation proceedings. 2024
Abstract
INTRODUCTION This study aimed to characterize patient risk groups and prognostic profiles to optimize clinical decision-making and guide appropriate medical cytomegalovirus (CMV) management among patients with allogeneic hematopoietic stem cell transplant (HSCT). METHODS Between 8/2021 and 2/2022, a 3-round modified Delphi study was conducted to generate consensus among 10 international experts in HSCT and infectious diseases. Experts were asked about treatment and prognoses for patients in 7 distinct clinical scenarios. Furthermore, experts were asked to risk-stratify patients by pre-/post-transplant characteristics. Consensus around opting for/against a treatment was observed if ≥75% or <25% of experts reported ≥50% likelihood to recommend or if treatments were ranked inside/outside the top 2 options and ≥75% of experts were within 1 SD of mean ranks. RESULTS Experts agreed on several unmet needs in CMV disease management post-HSCT, particularly avoidance of treatment-limiting toxicities with conventional CMV therapy and the emergence of both refractory and drug-resistant treatment failures. Experts considered CMV viral load, resistance profile, and route of administration as critical to treatment selection. For newer CMV therapeutic options, experts listed a lack of long-term use data, concerns over potential resistance, high cost, and limited availability as challenges restricting adoption and successful patient management. CONCLUSIONS Experts achieved consensus around patient risk stratifications and factors influencing therapeutic options. Recommendations emerging from this Delphi study may support practicing physicians when confronted with challenging CMV scenarios in patients with HSCT.
-
2.
[Allogeneic hematopoietic stem cell transplantation and treatment with CAR-T cells - identification of psycho-social vulnerability factors: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]
Polomeni, A., Ainaoui, M., Berr, A., de Bentzman, N., Denis, M., Friser, V., Magro, L., Yakoub-Agha, I.
Bulletin du cancer. 2023
Abstract
Allogeneic hematopoietic stem cell transplantation (HCT) and CAR-T cells therapy are treatments with curative aim for certain hematological malignancies, refractory or relapse. Nevertheless, they carry the risk of morbidity and mortality and may have a significant psychosocial impact, particularly for HCT. It is therefore necessary to identify psychological difficulties and social problems, as well as the patient's resources, and those of his entourage, in order to improve his overall management. The objective of this evaluation is not to pose contraindications to treatments, but to adapt the personalized care project. This identification must be carried out early on in the pre-HCT assessment journey to enable the implementation of appropriate actions by the various care providers. Based on a review of the literature, we designed a psychosocial data collection grid that can be initiated in pre-transplant and updated by accompanying the patient at each stage of follow-up (discharge from hospital, day-hospital follow-up, D100 evaluation). This grid is divided into 3 axes: socio-family context, psychological and somatic aspects. This tool allows the traceability of the interventions of different professionals and is a support for multidisciplinary exchanges.
-
3.
Genetic Findings of Potential Donor Origin following Hematopoietic Cell Transplantation: Recommendations on Donor Disclosure and Genetic Testing from the World Marrow Donor Association (WMDA): WMDA Guidelines on Genetic Findings of Donor Origin
Pryce, A., Van, E. E., Cody, M., Oakes, J., DeSalvo, A., Bannon, S., Burlton, C., Pawson, R., Fingrut, W., Barriga, F., et al
Transplantation and cellular therapy. 2023
-
-
-
Free full text
-
Editor's Choice
Abstract
Following hematopoietic cell transplantation, recipients are subjected to extensive genetic testing to monitor the efficacy of the transplant and identify relapsing malignant disease. This testing increasingly includes the use of large gene panels which may lead to incidental identification of genetic and molecular information of potential donor origin. Deciphering whether variants are of donor origin, and if so, whether there are clinical implications for the donor, can prove challenging. In response to queries from donor registries and transplant centers regarding best practice in managing donors when genetic mutations of potential donor origin are identified, the Medical Working Group of the World Marrow Donor Association established an expert group to review available evidence and to develop a framework to aid decision-making. These guidelines aim to provide recommendations on pre-donation consenting, post-donation testing of recipients and informing and managing donors when findings of potential donor origin are identified in recipients post-transplantation. It is recognised that registries will have different access to resources and financing structures. Therefore, where possible, we have made suggestions on how recommendations can be adapted.
PICO Summary
Population
An expert group convened by the Medical Working Group of the World Marrow Donor Association
Intervention
Provide recommendations on pre-donation consenting, post-donation testing of recipients
Comparison
None
Outcome
These guidelines aim to provide recommendations on pre-donation consenting, post-donation testing of recipients and informing and managing donors when findings of potential donor origin are identified in recipients post-transplantation.
-
4.
Management of patients with germline predisposition to haematological malignancies considered for allogeneic blood and marrow transplantation: Best practice consensus guidelines from the UK Clinical Genetics Group (UKCGG), CanGene-CanVar, NHS England Genomic Laboratory Hub (GLH) Haematological Malignancies Working Group and the British Society of Blood and Marrow Transplantation and cellular therapy (BSBMTCT)
Clark, A., Thomas, S., Hamblin, A., Talley, P., Kulasekararaj, A., Grinfeld, J., Speight, B., Snape, K., McVeigh, T. P., Snowden, J. A.
British journal of haematology. 2023
-
-
Free full text
-
Abstract
Germline predisposition to haematological cancers is increasingly being recognised. Widespread adoption of high-throughput and whole genome sequencing is identifying large numbers of causative germline mutations. Constitutional pathogenic variants in six genes (DEAD-box helicase 41 [DDX41], ETS variant transcription factor 6 [ETV6], CCAAT enhancer binding protein alpha [CEBPA], RUNX family transcription factor 1 [RUNX1], ankyrin repeat domain containing 26 [ANKRD26] and GATA binding protein 2 [GATA2]) are particularly significant in increasing the risk of haematological cancers, with variants in some of these genes also associated with non-malignant syndromic features. Allogeneic blood and marrow transplantation (BMT) is central to management in many haematological cancers. Identification of germline variants may have implications for the patient and potential family donors. Beyond selection of an appropriate haematopoietic stem cell donor there may be sensitive issues surrounding identification and counselling of hitherto asymptomatic relatives. If BMT is needed, there is frequently a clinical urgency that demands a rapid integrated multidisciplinary approach to testing and decision making involving haematologists in collaboration with Clinical and Laboratory Geneticists. Here, we present best practice consensus guidelines arrived at following a meeting convened by the UK Cancer Genetics Group (UKCGG), the Cancer Research UK (CRUK) funded CanGene-CanVar research programme (CGCV), NHS England Genomic Laboratory Hub (GLH) Haematological Oncology Malignancies Working Group and the British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT).
-
5.
Prospective clinical and biomarker validation of the ASTCT consensus definition for transplant-associated thrombotic microangiopathy (TA-TMA)
Ma, S., Bhar, S., Guffey, D., Kim, R. B., Jamil, M., Amos, C. I., Lee, S. J., Hingorani, S. R., Sartain, S. E., Li, A.
Transplantation and cellular therapy. 2023
Abstract
INTRODUCTION Transplantation-associated thrombotic microangiography (TA-TMA) is a disorder that causes severe complications post-allogeneic hematopoietic cell transplantation (allo-HCT). Diagnosing TA-TMA is challenging due to non-standardized criteria. In this study, we aimed to evaluate the new TA-TMA consensus definition from the American Society for Transplantation and Cellular Therapy (ASTCT) panel as part of an ongoing prospective pediatric cohort study and to compare the impact and outcomes of employing the current clinical TMA definition (cTMA) versus the new consensus definition. METHODS We included patients aged 0 to 18 years who underwent their first allo-HCT from May 2021 to January 2023 at Texas Children's Hospital. We compared the incidence, biomarkers, and outcomes of TA-TMA applying the previous and recently proposed screening algorithms and definitions. RESULTS While the classic microangiopathic hemolytic anemia (MAHA)-based cTMA definition led to an incidence of 12.7%, the ASTCT-HR definition doubled the incidence to 28.5% by day 100. In contrast to patients with concordant diagnosis (+/+) who had significantly worse post-transplant survival, those reclassified as TA-TMA by the new definition only (-/+) had significantly different prognosis (100% survival at day 100) despite the lack of TMA-directed therapy. Furthermore, biomarkers of the terminal and alternative complement pathways (sC5b9 and Ba, respectively) were significantly elevated around day 15 in the concordant group (+/+) but not in the discordant group (-/+) when compared to the non-TMA patients. CONCLUSIONS The recently proposed ASTCT consensus TA-TMA diagnosis is more sensitive and allows earlier recognition of manifestation that requires closer clinical monitoring but risks over-diagnosis and over-treatment. We recommend additional prospective validation.
-
6.
An ISCT Stem Cell Engineering Committee Position Statement on Immune Reconstitution: the importance of predictable and modifiable milestones of immune reconstitution to transplant outcomes
Bertaina, A., Abraham, A., Bonfim, C., Cohen, S., Purtill, D., Ruggeri, A., Weiss, D., Wynn, R., Boelens, J. J., Prockop, S.
Cytotherapy. 2022;24(4):385-392
Abstract
Allogeneic stem cell transplantation is a potentially curative therapy for some malignant and non-malignant disease. There have been substantial advances since the approaches first introduced in the 1970s, and the development of approaches to transplant with HLA incompatible or alternative donors has improved access to transplant for those without a fully matched donor. However, success is still limited by morbidity and mortality from toxicity and imperfect disease control. Here we review our emerging understanding of how reconstitution of effective immunity after allogeneic transplant can protect from these events and improve outcomes. We provide perspective on milestones of immune reconstitution that are easily measured and modifiable.
-
7.
[Relevance of antibodies in hematopoietic stem cell transplantation: Antibodies anti-HLA, anti-platelets, anti-granulocytes, anti-erythrocytes and anti-MICA. Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]
Delbos, F., Blouin, L., Bruno, B., Crocchiolo, R., Desoutter, J., Detrait, M., Nguyen-Lejarre, K. T., Giannoli, C., Lemarie, C., Renac, V., et al
Bulletin du cancer. 2020
Abstract
The presence of allo-antibodies in the serum of a recipient awaiting hematopoietic stem cell transplantation (HSCT) may have an impact on transfusion efficiency and/or donor choice, especially in the absence of an identical sibling donor. Prior to transplantation, donor specific anti-HLA (Human Leukocyte Antigen) antibodies (DSA) have a recognized effect on transplant outcome, correlated with the increasing MFI value and with the ability of such antibody to fix the complement fraction. Anti-platelet antibodies (anti-HLA class I and anti-HPA [Human Platelet Antigen]) are better involved in transfusion inefficiency and can be responsible for refractory status. ABO incompatibilities require a specific treatment of the graft in presence of high titer to avoid hemolytic adverse effects. Investigations of these antibodies should be carried out on a regular basis in order to establish appropriate transfusion recommendation, select an alternative donor when possible or adapt the source of cells. After transplantation, in case of delayed recovery or graft rejection, long term aplasia, persistent mixed chimerism or late release, and after elimination of the main clinical causes, a biological assessment targeted on the different type of antibodies will have to be performed in order to orient towards the cause or the appropriate therapy. Further studies should be carried out to determine the impact of anti-MICA antibodies and recipient specific anti-HLA antibodies, on the outcome of the transplantation.
-
8.
Use of chimerism analysis after allogeneic stem cell transplantation: Belgian guidelines and review of the current literature
Delie, A., Verlinden, A., Beel, K., Deeren, D., Mazure, D., Baron, F., Breems, D., De Becker, A., Graux, C., Lewalle, P., et al
Acta clinica Belgica. 2020;:1-9
Abstract
Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option in both adult and pediatric patients with malignant and non-malignant hematological diseases. Chimerism analysis, which determines the donor or recipient origin of hematopoietic cells in HSCT recipients, is an essential aspect of post-HSCT follow-up.Objectives: To review the current literature and develop Belgian consensus guidelines for the use of chimerism analysis in the standard of care after allogeneic HSCT.Methods: Non-systematic review of the literature in consultancy with the members of the BHS transplantation committee.Results: Clinical application with regards to prediction of graft failure or relapse as well as cell source are reviewed. A consensus guideline on the use of chimerism analysis after HSCT is presented.Conclusion: Monitoring of the dynamics or kinetics of a patient's chimerism status by serial analysis at fixed time points, as well as on suspicion of relapse or graft failure, is needed to monitor engraftment levels, as well as disease control and possible relapse.
-
9.
Next-generation sequencing for BCR-ABL1 kinase domain mutations in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A position paper
Soverini, S., Albano, F., Bassan, R., Fabbiano, F., Ferrara, F., Foa, R., Olivieri, A., Rambaldi, A., Rossi, G., Sica, S., et al
Cancer medicine. 2020
Abstract
Emergence of clones carrying point mutations in the BCR-ABL1 kinase domain (KD) is a common mechanism of resistance to tyrosine kinase inhibitor (TKI)-based therapies in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Sanger sequencing (SS) is the most frequently used method for diagnostic BCR-ABL1 KD mutation screening, but it has some limitations-it is poorly sensitive and cannot robustly identify compound mutations. Next-generation sequencing (NGS) may overcome these problems. NSG is increasingly available and has the potential to become the method of choice for diagnostic BCR-ABL1 KD mutation screening. A group discussion within an ad hoc constituted Panel of Experts has produced a series of consensus-based statements on the potential value of NGS testing before and during first-line TKI-based treatment, in relapsed/refractory cases, before and after allo-stem cell transplantation, and on how NGS results may impact on therapeutic decisions. A set of minimal technical and methodological requirements for the analysis and the reporting of results has also been defined. The proposals herein reported may be used to guide the practical use of NGS for BCR-ABL1 KD mutation testing in Ph+ ALL.
-
10.
Clinical practice recommendation on hematopoietic stem cell transplantation for acute myeloid leukemia patients with FLT3 internal tandem duplication: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Bazarbachi, A., Bug, G., Baron, F., Brissot, E., Ciceri, F., Abou Dalle, I., Dohner, H., Esteve, J., Floisand, Y., Giebel, S., et al
Haematologica. 2020
Abstract
The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in 25-30% of patients with acute myeloid leukemia . Because of the poor prognosis associated with FMS-like tyrosine kinase 3 internal tandem duplication mutated Acute myeloid leukemia, allogeneic-hematopoietic stem-cell transplantation was commonly performed in first complete remission. Remarkable progress has been made in frontline treatments with the incorporation of FLT3 inhibitors and the development of highly sensitive minimal/measurable residual disease assays. Similarly, recent progress in allogeneic-hematopoietic stem-cell transplantation includes improvement of transplant techniques, the use of haplo-identical donors in patients lacking an HLA matched donor, and the introduction of FLT3 inhibitors as posttransplant maintenance therapy. Nevertheless, current transplant strategies vary between centers and differ in terms of transplant indications based on the internal tandem duplication allelic ratio and concomitant nucleophosmin-1 mutation, as well as in terms of post-transplant maintenance/consolidation. This review generated by international leukemia or transplant experts, mostly from the European Society for Blood and Marrow Transplantation, attempts to develop a position statement on best approaches for allogeneic-hematopoietic stem-cell transplantation for acute myeloid leukemia with FMS-like tyrosine kinase internal tandem duplication including indications and modalities of allogeneic-hematopoietic stem-cell transplantation and on potential optimization of post-transplant maintenance with FMS-like tyrosine kinase inhibitors.