Somatic, hematologic phenotype, long‐term outcome, and effect of hematopoietic stem cell transplantation. An analysis of 97 Fanconi anemia patients from the Italian national database on behalf of the Marrow Failure Study Group of the AIEOP (Italian Association of Pediatric Hematology–Oncology)

Abstract

We analyzed 97 Fanconi anemia patients from a clinic/biological database for genotype, somatic, and hematologic phenotype, adverse hematological events, solid tumors, and treatment. Seventy‐two patients belonged to complementation group A. Eighty percent of patients presented with mild/moderate somatic phenotype and most with cytopenia. No correlation was seen between somatic/hematologic phenotype and number of missense mutations of FANCA alleles. Over follow‐up, 33% of patients improved or maintained mild/moderate cytopenia or normal blood count, whereas remaining worsened cytopenia. Eleven patients developed a hematological adverse event (MDS, AML, pathological cytogenetics) and three developed solid tumors. 10 years cumulative risk of death of the whole cohort was 25.6% with median follow‐up 5.8 years. In patients eligible to hematopoietic stem cell transplantation because of moderate cytopenia, mortality was significantly higher in subjects transplanted from matched unrelated donor over nontransplanted subjects, whereas there was no significant difference between matched sibling donor transplants and nontransplanted patients. In patients eligible to transplant because of severe cytopenia and clonal disease, mortality risk was not significantly different in transplanted from matched unrelated versus matched sibling donor versus nontransplanted subjects. The decision to transplant should rely on various elements including, type of donor, HLA matching, patient comorbidities, impairment, and clonal evolution of hematopoiesis. Am. J. Hematol. 91:666–671, 2016. © 2016 Wiley Periodicals, Inc.

Transplant results in adults with Fanconi anaemia

“…Our results raise several important issues: should all FA patients with signs of BM failure undergo HSCT at a young age? This concern is supported by a number of observations: Svahn et al () recently described a fairly large Italian patient cohort in which 33% of patients improved or maintained mild‐to‐moderate cell counts over time, illustrating the uncertain course of BM failure in a substantial subgroup of FA patients. Secondly, there remains a risk of transplant‐related mortality (TRM), even at a young age.…”

“…Graft‐versus‐host disease should be avoided in these FA patients, especially as it raises the risk for secondary malignancies (Svahn et al , ). Our data indicate that both acute and chronic GvHD are important issues.…”

Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study

“…Outcomes for the younger patients without MDS are comparable with outcomes of matched-sibling donor HCT for FA. 16,18,19,22 Increasingly better survival after HCT for FA increases the importance of minimizing late consequences of transplant caused by the risk of subsequent malignancies. Radiation exposure and GVHD are the 2 main HCT-related factors that increase the risk of subsequent malignancies.…”

“…11,[13][14][15] Improved outcomes led to the elimination of total body irradiation (TBI) from the preparative regimen for FA HCT using fully matched sibling donors in the past decade. [16][17][18][19] With improved HCT outcomes, more patients with FA have survived to adulthood, [20][21][22] and long-term side effects of HCT, including the increased risk of secondary cancers have become critical considerations for long-term care.…”

How I manage patients with Fanconi anaemia

“…In a recent survey on a large Italian FA population, the proportion of patients displaying a mild somatic phenotype (aesthetic malformations neither affecting organ function nor requiring correction) outnumbered (43·3%) that of patients with moderate (37·1%) or severe (19·6%) somatic phenotype. Mild and moderate phenotype patients were diagnosed later because of marrow failure whereas those with a severe phenotype were diagnosed earlier because of malformations also without marrow failure (Svahn et al , ). This suggests that the diagnosis of FA is easier to determine if malformations are also present in the absence of bone marrow failure, but also that it should be considered when marrow failure with or without minor somatic malformations occurs.…”