Occurrence of colon tumors in a 16-year-old Japanese boy after hematopoietic stem cell transplantation for Diamond Blackfan anemia at age of 4: a case report.

Diamond Blackfan anemia (DBA) is a congenital pure red cell aplasia mainly caused by a mutation in ribosomal protein genes. One of the proposed mechanisms for red cell aplasia in DBA is apoptosis caused by constitutive activation of tumor suppressor TP53 protein following defective ribosome biogenesis. Because of this close relationship between ribosome biogenesis and TP53 activation, patients with DBA are considered to be cancer-prone. The association between bone marrow failure and tumor susceptibility in DBA appears paradoxical. Also, the detailed information is lacking on malignancy occurring in patients with DBA. Here, we report a case of a 16-year-old Japanese boy suffering from multiple colon tumors during the follow-up after hematopoietic stem cell transplantation for DBA at the age of 4. Well differentiated tubular adenocarcinoma was detected at the rectum 12 years after the transplantation, followed by multiple tubular adenomas of low to high grade throughout the colon. Endoscopic submucosal dissection was performed for these tumors and the lesions were completely resected. These tumors did not show diffuse and strong TP53 positivity by immunohistochemistry, suggesting that TP53 mutation was not involved in the tumorigenesis as observed in conventional colorectal cancers. Microsatellite instability test and immunohistochemical examination of ß-catenin and MLH1 proteins of these tumors showed that WNT signaling or microsatellite instability was less likely to be involved in the present tumors as observed in conventional left-sided or right-sided colon cancers, respectively. To our knowledge, this is the first case report of colon tumors associated with DBA.

Trasplante alogénico de precursores hematopoyéticos de sangre de cordón umbilical de donante no emparentado: primera experiencia, en tres casos, con donantes del banco público chileno de células de cordón / Allogenic hematopoietic stem cell transplantation with unrelated cord blood: Report of three cases from the Chilean cord blood bank

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

[Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank]. / Trasplante alogénico de precursores hematopoyéticos de sangre de cordón umbilical de donante no emparentado: primera experiencia, en tres casos, con donantes del banco público chileno de células de cordón.

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

Normalization of red cell enolase level following allogeneic bone marrow transplantation in a child with Diamond-Blackfan anemia.

We describe a girl with Diamond-Blackfan anemia with accompanying red cell enolase deficiency. At the age of 9 yr old, the patient received allogeneic bone marrow transplantation from her HLA-identical sister who had normal red cell enolase activity. While the post transplant DNA analysis with short tandem repeat has continuously demonstrated a stable mixed chimerism on follow-up, the patient remains transfusion independent and continues to show a steady increase in red cell enolase activity for over two and a half years following bone marrow transplantation.

Hematopoietic stem cell transplantation for Diamond-Blackfan anemia: a report from the Aplastic Anemia Committee of the Japanese Society of Pediatric Hematology.

Transfusion-dependent Diamond-Blackfan anemia (DBA) patients opt for allogeneic hematopoietic stem cell transplantation (HSCT) as curative therapy. Clinical outcomes of 19 transplanted Japanese patients were analyzed. Prior to HSCT, 10 patients (53%) suffered hemosiderosis with organ dysfunction, and all eight with short stature (42%) had adverse effects of prednisolone. Median age at the time of HSCT was 56 months. Transplantation sources were 13 bone marrow [six human leukocyte antigen (HLA)-matched siblings, and six HLA-matched and one HLA-mismatched unrelated donors], five cord blood (two HLA-matched siblings and three HLA-mismatched unrelated donors), and one peripheral blood from haploidentical mother. All 13 patients with bone marrow transplantation (BMT) and two with sibling cord blood transplantation (CBT) had successful engraftment. Of three patients who underwent unrelated CBT, one died after engraftment, and the other two had graft failure but succeeded in a second BMT from an HLA-disparate father and unrelated donor, respectively. One died shortly after haploidentical PBSCT. The five-yr failure-free survival rate after BMT was higher than CBT (100%: 40%, p=0.002). Platelet recovery was slower in seven unrelated BMT than in six sibling BMT (p=0.030). No other factors were associated with engraftment and survival. These results suggest that allogeneic BMT, but not unrelated CBT, is an effective HSCT for refractory DBA.

Preimplantation genetics: Improving access to stem cell therapy.

There has been progress in the application of stem cell transplantation for treatment of an increasing number of severe congenital and acquired bone marrow disorders, currently restricted by the availability of human leukocyte antigen (HLA)-matched related donors. Preimplantation HLA typing has recently been introduced to improve the access to stem cell therapy for inherited bone marrow failures. Preimplantation genetic diagnosis (PGD) provides an option not only for avoiding an affected pregnancy with thalassemia and other inherited disorders but also for preselection of the HLA-compatible donors for affected siblings. Multiple short tandem repeat markers throughout the HLA region are applied for this purpose, allowing 100% accuracy of HLA typing, through picking up possible recombination in the HLA region, as well as the copy number of chromosome 6, which affect accuracy of preimplantation HLA typing. Present experience of preimplantation HLA typing includes preimplantation HLA typing in 180 cycles, 122 of which were done as part of PGD for Fanconi anemia, thalassemia, Wiscott-Aldrich syndrome, hyper-immunoglobulin M syndrome, hypohidrotic ectodermal dysplasia with immune deficiency, and X-linked adrenoleukodystrophy, and 58 for the sole purpose of HLA typing for leukemias and for aplastic and Diamond-Blackfan anemia. The applied method resulted in the accurate preselection and transfer of 100% HLA-matched embryos, yielding already three dozen clinical pregnancies and the birth of two dozen HLA-matched children to the siblings requiring stem cell transplantation. Successful therapy with HLA-matched stem cells, obtained from these PGD children, has been achieved already for Diamond-Blackfan anemia hypohidrotic ectodermal dysplasia with immune deficiency and thalassemia.

Allogeneic peripheral blood stem cell transplant (PBSCT) using anti-IL2 receptor antibody Daclizumab for the prevention of acute graft versus host disease in steroid refractory Diamond Blackfan anaemia: a case report.

The case report of a 2 year old boy with steroid refractory DBA, treated with allogeneic PBSCT from an HLA matched sibling is presented. Anti-IL2 receptor antibody Daclizumab was used as a prophylaxis for graft versus host disease (GvHD). Complete recovery without any evidence of GvHD ensued.