Consensus of German Transplant Centers on Hematopoietic Stem Cell Transplantation in Fanconi Anemia

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative therapy for the severe hematopoietic complications associated with Fanconi anemia (FA). In Germany, it is estimated that 10?15 transplants are performed annually for FA. However, because FA is a DNA repair disorder, standard conditioning regimens confer a high risk of excessive regimen-related toxicities and mortality, and reduced intensity regimens are linked with graft failure in some FA patients. Moreover, development of graft-versus-host disease is a major contributing factor for secondary solid tumors. The relative rarity of the disorder limits HSCT experience at any single center. Consensus meetings were convened to develop a national approach for HSCT in FA. This manuscript outlines current experience and knowledge about HSCT in FA and, based on this analysis, general recommendations reached at these meetings.

Hematopoietic Stem Cell Transplantation in a Child With Fanconi Anemia – Case Report

“…3,6 Preživljenje pacijenata s FA kod kojih je uči-njen TKMS od HLA-podudarnoga srodnog darivatelja vrlo je dobro i, prema izvješćima, može iznositi i 90% nakon 10 godina. 7,8 Optimalnim uvjetima za provođenje TKMS-a od srodnog darivatelja smatraju se rana dob (prije 9. godine života), nevelik prethodni broj (< 20) transfuzija eritrocita i/ili trombocita, neprovođenje terapije androgenima i izostanak razvoja MDS-a ili leukemije.…”

“…6 Naš je tim za našeg bolesnika odlučio primijeniti protokol takvog tipa prema "Konsenzusu njemačkih transplantacijskih centara o transplantaciji krvotvornih matičnih stanica u Fanconijevoj anemiji", koji je nastao na temelju usporedbe višegodišnjih studija pod nazivom protokoli GEFA (German Fanconi Anemia). 3 Osim sniženja rizika od kasnije pojave nehematoloških maligniteta, izbjegavanje zračenja u protokolu kondicioniranja također poboljšava kvalitetu života bolesnika reducirajući kasne posttransplantacijske komplikacije poput neplodnosti, endokrinih poremećaja, pojave katarakte i drugih oštećenja. Zračenje se s dobrim rezultatima zamjenjuje primjenom alkilirajućeg agensa busulfana.…”

“…5 Uz karakteristična fenotipska obilježja i pancitopeniju, najvažnije obilježje pacijenata s FA jest povišen rizik od razvoja malignih bolesti, i hematoloških (mijelodisplastični sindrom (MDS) i akutna mijeloična leukemija (AML)) i nehematoloških (karcinomi pločastih stanica u području glave, vrata, jednjaka, vulve, anusa i cerviksa). 3,5 Učestalost malignih bolesti i poremećaja koštane srži raste s dobi, a iznosi 30% za maligne bolesti i 90% za poremećaj koštane srži u pacijenata starih do 40 Summary. Fanconi anemia (FA) is a rare inherited disorder associated with congenital abnormalities, progressive bone marrow failure and a predisposition for hematological and nonhematological malignant disease.…”

Allogeneic Stem Cell Transplantation after Fanconi Anemia Conditioning in Children with Ataxia-Telangiectasia Results in Stable T Cell Engraftment and Lack of Infections despite Mixed Chimerism

“…fludarabine at 30 mg/m 2 daily from days À8 to À3 (total dose, 180 mg/m 2 ), and i.v. antithymocyte globulin (ATG)-Fresenius at 20 mg/kg body weight daily from days À3 to À1 [10]. The modification of the conditioning protocols in the first patient with A-T was due to the replacement of oral busulfan with the i.v.…”

Allogeneic-matched sibling stem cell transplantation in a 13-year-old boy with ataxia telangiectasia and EBV-positive non-Hodgkin lymphoma

“…With AT being a cancer predisposition syndrome, it remains unclear whether HSCT containing alkylating agents will result in the earlier development of consecutive malignancies as has been suggested for Fanconi anemia. 17 …”