Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Cell Transplantation for Inherited Bone Marrow Failure Syndromes: Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation

Abstract

Fanconi anemia (FA), dyskeratosis congenita (DC), and Diamond Blackfan anemia (DBA) are 3 of the most common inherited bone marrow failure syndromes (IBMFS), in which the hematologic manifestations can be cured with hematopoietic cell transplantation (HCT). Later in life, these patients face a variety of medical conditions, which may be a manifestation of underlying disease or due to pre-HCT therapy, the HCT, or a combination of all these elements. Very limited long-term follow-up data exist in these populations, with FA the only IBMFS that has specific published data. During the international consensus conference sponsored by the Pediatric Blood and Marrow Transplant Consortium entitled “Late Effects Screening and Recommendations following Allogeneic Hematopoietic Cell Transplant (HCT) for Immune Deficiency and Nonmalignant Hematologic Disease” held in Minneapolis, Minnesota in May of 2016, a half-day session was focused specifically on the unmet needs for these patients with IBMFS. A multidisciplinary group of experts discussed what is currently known, outlined an agenda for future research, and laid out long-term follow-up guidelines based on a combination of evidence in the literature as well as expert opinion. This article addresses the state of science in that area as well as consensus regarding the agenda for future research, with specific screening guidelines to follow in the next article from this group.

Pediatric Diamond‐Blackfan anemia in the Netherlands: An overview of clinical characteristics and underlying molecular defects

“…Historically, HSCT in DBA has been controversial with significant treatment‐related mortality risks and a favorable outcome for younger children (<10 years) who were transplanted with an HLA‐identical sibling donor in particular . In this study, HSCT was successful in 6 of 6 patients, including patients older than 10 years of age, and with the use of unrelated donor stem cells. While long‐term outcome data in our patient population are not available yet, and our sample size is small, these data do suggest that allogeneic HSCT in pediatric DBA can be performed successfully with acceptable risks.…”

Long-Term Follow-Up of a Case with Dyskeratosis Congenita Caused by NHP2-V126M/X154R Mutation: Genotype-Phenotype Association

“…However, underlying pulmonary and hepatic disease/sensitivity may predispose these patients to an increased risk of late complications of HCT such as vascular, pulmonary, and liver complications [1]. Reduced intensity conditioning tends to decrease the risk of developing a pulmonary complication, which is the main cause of late mortality in these patients [12]. Our patient will be followed up carefully for the expected HCT complications and the clinical features of DC.…”

ATG Based Conditioning Regimen in Stem Cells Transplantation of Fanconi Anemia: A Single Center Experience of 63 Patients

“…In the past, it was reported that the combination of alkylating agents and irradiation previously used for conditioning of acquired aplastic anemia led to unacceptable toxicity in FA patients [23]. So according to these data, the conditioning protocol was modifi ed by reducing the doses of cyclophosphamide and/or irradiation, resulting in a dramatic decrease of TRMs [24].…”