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CD34-enriched peripheral stem cells infusion for graft insufficiency treatment in a pediatric patient with severe aplastic anemia after allogeneic bone marrow transplantation

Bone Marrow Transplantation volume 34, pages 465–466 (2004)Cite this article

Allogeneic transplantation of hematopoietic stem cells is a treatment of choice for patients with severe acquired aplastic anemia, who have an HLA-identical family donor. This treatment is now able to cure 80–90% of young SAA patients.1 Meanwhile, early and late graft failure still remains a major problem, compromising the survival of these patients, and often leads to second allogeneic stem cell transplantation from the same or an alternative donor.1, 2 The intensification of the preparative regimen and the use of high doses of stem cells have led to further reduction of the graft failure rate, but the problem is still unpredictable. Moreover, deep immunosuppression associated with second-transplant procedure and graft-versus-host disease (GVHD) onset may further decrease the survival rate of this category of patients. We report about a pediatric SAA patient with transient engraftment after allogeneic bone marrow transplantation (BMT), compromised with acute GVHD, who received a CD34-selected stem cells boost from the same donor and achieved full donor chimerism and stable hematopoietic reconstitution.

A 14 year-old girl presented with very severe acquired aplastic anemia in September 2002. Fanconi Anemia and PNH were ruled out by appropriate diagnostic methods. In November 2002, the patient underwent allogeneic BMT from a HLA-matched sibling donor. Patient and donor characteristics are shown in Table 1. The conditioning regimen consisted of cyclophosphamide (50 mg/kg/day on days –5 to –2) and antithymocyte globulin (ATGAM, 30 mg/kg/day on day –3 to day −1). On day 0, the patient received unmanipulated bone marrow (NC – 3.2 × 108/kg, MNC – 1 × 108/kg). GVHD prophylaxis included cyclosporin A and a short course of methotrexate. Engraftment was delayed till day +27; the patient remained dependent on blood component transfusions till day +34. Acute GVHD of the skin (grade 2) and liver (grade 1) developed on day +45 post BMT and was successfully controlled with methylprednisolone and CsA. On day +50, the patient's blood count revealed hemoglobin 84 g/l, leukocytes 1.8 × 106/l with PMN less than 0.6 × 106/l, and 16 × 106 platelets/l. The patient started stimulation with G-CSF, but there was no evidence of hematological improvement after 4 weeks of treatment with the growth factor. Chimerism analysis based on sex chromosome polymorphism was carried out on day +80, and 95% of donor cells were discovered despite hypocellular bone marrow aspirate and high transfusion dependency. Blood count performed on day +80 revealed hemoglobin 89 g/l, leukocytes 1.5 × 106/l, and 19 × 106 platelets/l. There were no confirmations of CMV, HHV-6 or Parvovirus infection by qualitative PCR technique. On day +100, the patient underwent a boost of CD34-enriched stem cells from the same donor. After a 5-day mobilization with G-CSF, a single apheresis product was T-cell-reduced using the CliniMACS sorting device (Miltenyi Biotech, Gladbach, Germany). The transplant contained 9 × 106/kg CD 34+ cells, and 1 × 108/kg CD3+ cells were added to enhance engraftment. GVHD prophylaxis consisted of basiliximab and mofetil mycophenolate. Pancytopenia gradually improved over the next 3 weeks after a second infusion of stem cells, the patient became transfusion independent. Acute GVHD grade 2 (skin/grade 1/and gut/grade 1) reappeared on the day +151/+54 and was treated successfully with steroids. A chimerism study performed 3 months post second CD34-enriched PBSC infusion showed all bone marrow cells to be of donor origin. Now, 16 months after the first transplantation, the patient remains alive and well, with full hematological reconstitution and without evidence of GVHD.

Table 1 Patient and donor characteristics
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Acknowledgements

We thank Dr Chiara De Luka for her assistance in preparation of the manuscript.

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  1. Bone Marrow Transplantation Unit, Russian Institute for Pediatric Hematology, Moscow, Russia

    P Trakhtman, I Shipicina, D Balashov, J Scvortsova, Z Dishlevaja, O Blagonravova & A Maschan

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Trakhtman, P., Shipicina, I., Balashov, D. et al. CD34-enriched peripheral stem cells infusion for graft insufficiency treatment in a pediatric patient with severe aplastic anemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 34, 465–466 (2004). https://doi.org/10.1038/sj.bmt.1704599

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