G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion: an excellent alternative for high-risk leukemia

Abstract

Summary:Based on our encouraging results of G-CSF-primed HLA-matched related marrow transplants for high-risk leukemia, we extended the study from matched related to haploidentical transplants using G-CSF primed marrow and sequential immunosuppressants to prevent both graft-versus-host disease (GVHD) and host-versusgraft rejection (HVGR). Fifteen high-risk leukemia patients, who needed urgent transplantation but lacked an HLA-matched donor, underwent G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion. Donors were given G-CSF (Lenograstim) at 3-4 g/kg/day for 7 days prior to marrow harvest. GVHD and HVGR prophylaxis were combined in the sequential usage of cyclosporin A, methotrexate, anti-thymocyte globulin and mycophenolate mofetil. All patients established sustained trilineage engraftment at a median of 19 days and 21 days for neutrophil and platelets respectively. G-CSF priming significantly increased CD34 + and CFU-GM cells, reduced total lymphocytes and reversed the CD4 + /CD8 + ratio in the donor marrow. The incidence of grade II-IV acute GVHD was 33.3%. Nine patients survived more than a year with a Karnofsky performance status of 100%. Estimated overall disease-free survival at 2 years was 60 ؎ 7%. In conclusion, using G-CSF priming marrow grafts along with sequential immunosuppressants provided an excellent alternative for the treatment of high-risk hematological malignancy in patients who lack matched donors.

G-CSF-primed BM for allogeneic SCT: revisited

“…Therefore, it was concluded that GBM from haploidentical-mismatched sibling donors can be an excellent alternative for the treatment of high-risk hematological patients lacking matched donors. 95 Similar conclusions were also reported for 45 patients with high-risk AML, who received unmanipulated GBM from haploidentical sibling donors. 96 …”

Good outcome of haploidentical hematopoietic SCT as a salvage therapy in children and adolescents with acquired severe aplastic anemia

“…18 The incidence of aGVHD was only 6.3% in G-BM transplants compared with 33% in steady-state marrow transplants. 19 (2) Mixtures of G-PB and G-BM have successfully introduced T-cell hyporesponsiveness, polarization of T cells from Th1 to Th2 and protected from aGVHD. 20 (4) Higher-dose stem cell numbers may be given via a combination of G-BM and G-PBSC than via BM or PB alone to overcome the harmful effect of ATG on hematopoiesis.…”

Overcoming various comorbidities by G-CSF-primed unmanipulated BM SCT in adult patients with AML

“…To promote rapid engraftment while avoiding detrimental chronic GVHD, several previous studies have investigated megadose SCT using pBM plus PBSCs 10 and high-dose pBM. 5,6,8,11 On the basis of these earlier studies, we investigated the use of pBM in allogeneic sibling SCT under less than optimal conditions. More specifically, we examined the effectiveness of this procedure in cases of inferior donor condition (that is, markedly lower body weight than the recipient) and in recipients exhibiting various clinical comorbidities.…”