Since the introduction of combined immunosuppressive therapy (IST) into management of aplastic anemia (AA) in childhood response and probability of survival improved. In contrast to bone marrow transplantation (BMT), however, patients after IST are not considered cured as high rates of relapse and development of clonal disease demonstrate. From 11/93 to 9/97 114 children (65 m, 49 f; median age 9.5 y.) from 37 centers in Germany and Austria were registered in the SAA 94 study. 86 patients lacking a matched sibling donor received IST. Most of the patients suffered from very severe (VSAA: PMN < 200/microliter) or severe AA (SAA: PMN < 500/microliter). All patients were treated with combined IST consisting of ALG and Cyclosporin A (CSA). VSAA and SAA patients were additionally treated with G-CSF. Therapy response was evaluated at day 112, after 6, 12 and 18 months. 8/86 patients died, the probability of survival being 87% after 4 years. At d 112 61% of evaluable patients became independent of transfusions (IST response: CR + PR), 13% with normal blood counts (CR). After 6 months 33% showed CR. At 12 and 18 months response improved to 74% resp. 80%, 39% resp. 55% CR. The best response was achieved in the subgroup of VSAA with 90% (PR + CR) and 65% CR after 18 months. 4 patients developed AML 3-19 months after the beginning of IST. In 2/4 pts. an aberrant clone (-7; 5q-) could be detected retrospectively in BM at diagnosis of AA. 3 nonresponders developed chromosomal aberrations (+19; -7, +12; +8) after 4, 12 and 16 months without morphological signs of AML or MDS. Overall 11 relapses occurred at a median time of 12 months (range 5-27 months) after the beginning of IST. 2 of them relapsed under CSA therapy, 2 under tapering of CSA and 7 after cessation of CSA. 7 patients responded again to CSA monotherapy. Overall response rate is 77% with a probability of event free survival (EFS) of 54% after 4 years regarding all complications mentioned as events.

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Congenital amegakaryocytic thrombocytopenia (CAT), a rare syndrome with failure of megakaryopoiesis, cannot be cured by immunoglobulins, steroids or cyclosporin, but only by allogeneic bone marrow transplantation (BMT). We report on eight patients with CAT, all of whom were dependent at the time of BMT on platelet transfusion. Sources of haematopoietic progenitor cells were bone marrow (n = 5), peripheral stem cells (n = 2) and cord blood (n = 1). Seven patients engrafted. Both patients with matched unrelated donor transplants died, six patients are well with stable platelet counts 3–27 months after transplantation. BMT represents a curative option for CAT. The benefit of using alternative marrow donors should be carefully evaluated.

Summary:A 14-year-old girl developed very severe aplastic anemia unresponsive to steroids, cyclosporine, ATG and filgrastim. She experienced repeated bacterial infections, hypermenorrhagia and epistaxis and received numerous transfusions. Lacking a matched family or unrelated donor, she was transplanted 6 months after diagnosis with CD34 + cell-enriched peripheral stem cells from her HLA-haploidentical uncle. Conditioning included fludarabine, cyclophosphamide, 800 cGy TLI and OKT3. Prompt and sustained trilineage engraftment occurred. Acute GVHD grade 1 and herpes esophagitis were successfully treated. Eight months after grafting she was well with stable hematopoiesis. She then succumbed to fulminant hepatic failure due to adenovirus infection. Bone Marrow Transplantation (2001) 27, 111-113.

Summary:Allogeneic peripheral stem cell transplantation in six children with non-malignant hematologic or metabolic diseases which are eventually fatal was carried out with parental donors. Given three to five HLA mismatches, all grafts underwent CD34 ؉ cell selection as graftversus-host prophylaxis. The patients received median doses of 16.7 ؋ 10 6 CD34 ؉ cells/kg and 1.2 ؋ 10 4 CD3 ؉ cells/kg. All transplants engrafted. Neutrophils Ͼ0.5/nl were reached on day 11 (9-19) and platelets Ͼ50/nl on day 13 (10-25). Acute GVHD responding to steriods occured in three of six patients; it was restricted to the skin and overall did not exceed grade I. Two patients died of viral infections and four are alive with stable blood counts for 13, 15, 25 and 26 months. For children with non-malignant diseases which will eventually be fatal and which can be cured or ameliorated by allogeneic BMT, CD34 ؉ -selected stem cell transplants from mismatched or even haploidentical parents can be used if no other suitable donor is available. With high CD34 ؉ cell doses and low CD3 ؉ cell numbers, engraftment and avoidance of acute GVHD can be expected. Infections after transplantation remain the primary threat to survival. Bone Marrow Transplantation (2002) 29, 9-13.