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EBMT 2021 Annual Meeting - Transplantation and bone marrow failure in 2021

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Workshop: W05 Transplantation and bone marrow failure in 2021

Wednesday, March 17, 09:15 - 10:30, Auditorium 2

In this four-part session on transplantation and bone marrow failure in 2021, Dr Amy DeZern (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital, Baltimore, MD, USA) will discuss haploidentical HSCT and aplastic anaemia.

In this presentation, she reviews the needs of patients with severe aplastic anaemic (SAA) for optimal therapy. “The treatment should be widely available and allow rapid recovery of haematopoiesis with low treatment-related mortality,” she explains.  “Additionally, the approach should eliminate risk of relapse and secondary clonal disease.”

Dr DeZern will present the data from Johns Hopkins on the use of haploidentical bone marrow transplant (BMT) for SAA with intensive graft versus host disease (GVHD) prophylaxis including post-transplant cyclophosphamide. She reviews the outcomes to date for 27 patients with relapsed/refractory disease as well as 26 patients with treatment-naïve SAA.  She also includes use of unrelated donors and the identical conditioning where needed.

The data show excellent disease-free survival and extremely low rates of acute and chronic GVHD with limited mortality.  Dr DeZern concludes with her support for use of nonmyeloablative haplo BMT in SAA as a paradigm shift, so that all patients can proceed quickly to safe, curative BMT.

Following this, a presentation on Fanconi Anaemia (FA) will be given by Professor Carmem Bonfim, Director of the Pediatric Blood and Marrow Transplantation Program at the Hospital Pequeno Príncipe and Professor of the post-graduation program at the Federal University of Parana, Curitiba, PR, Brazil.

She explains: “FA is a rare disease characterised by genomic instability, progressive bone marrow failure, congenital abnormalities, and a striking predisposition for the development of cancer.”

Haematopoietic cell transplantation (HCT) offers cure for the haematological complications of FA. Young patients in aplasia transplanted from HLA-matched related or unrelated donors have an excellent survival. For patients without a compatible donor, in vitro T-cell depletion of the graft is effective in eliminating severe acute and chronic GvHD; however, this requires techniques that are not widely available.

“During this talk I will present the outcome of 63 FA patients transplanted from T-cell-replete haploidentical donors using a modified post-transplantation cyclophosphamide platform,” says Professor Bonfim.  Her team reports a better 1-year overall survival for patients receiving serotherapy (rabbit-ATG or alemtuzumab) in the preparatory regimen compared to those without serotherapy (87% vs 64%; p:0.01).

She concludes: “The incidence of severe acute and chronic GvHD significantly decreased after the introduction of serotherapy. When serotherapy was combined with a selection of the haplo donor based on recent guidelines, we observed a further reduction in the incidence of chronic GvHD. Although results are very promising, immune reconstitution is delayed in the alemtuzumab group and longer follow-up is still needed to better identify late outcomes.”  

HSCT in Diamond-Blackfan Anaemia (DBA) is the subject of the final talk given by paediatric haematologist and oncologist Dr Brigitte Strahm of the University of Freiburg, Germany.

She explains: “DBA is a rare inherited bone marrow failure syndrome caused by mutations or less frequently deletions in genes coding for ribosomal proteins. In 30% of patients no genetic aberration is identified. Patients usually present with transfusion-dependent macrocytic anaemia in early infancy. DBA is also recognised as being a cancer predisposition syndrome (osteogeneic sarcoma, colon cancer).”

About 60% of patients respond to an initial course of steroids. Patients aged under one year or steroid non-responders are treated with red blood cell transfusions and chelation. About 20% become transfusion independent without any further treatment.

Dr Strahm explains that HSCT is the only curative approach for the haematological manifestations. Transfusion dependency (steroid NR, - intolerance, - dependency), alloimmunisation, chelator toxicity, progressive pancytopenia or MDS/AML are indications for HSCT. She discusses that HSCT from a MSD has resulted in an overall survival of above 80% and is recommended for all indications. Sibling donors should carefully be evaluated to rule out a silent carrier status.

Recent reports describe an improved outcome of MUD HSCT with an overall survival in the range 74-90% and the given indications may be extended to MUD. Age of under 10 years and iron overload are risk factors for a worse outcome including a higher incidence of chronic GvHD.

Dr Strahm concludes: “The majority of transplants reported have been performed with a myeloablative conditioning and a standard regimen including busulfan or treosulfan had been recommended. However, additional data indicates that a reduced toxicity regimen of treosulfan and fludarabine is associated with less toxicity and good sustained engraftment. In future, gene therapy might be a therapeutic option for patients with DBA.”

In the other presentation in this session, paediatric haematologist Professor Jean-Hugues Dalle (HSCT program director, Robert-Debre Hospital & Paris Diderot University, France) will give a talk on upfront transplantation in aplastic anaemia.