We compared the outcomes of allogeneic hematopoietic stem cell transplantation using reduced intensity and myeloablative conditioning for the treatment of patients with advanced hematological malignancies. A total of 75 adult patients received transplants from human leukocyte antigen-matched donors, coupled with either reduced intensity (n=40; fludarabine/melphalan, 28; fludarabine/cyclophosphamide, 12) or myeloablative conditioning (n=35, busufan/cyclophosphamide). The patients receiving reduced intensity conditioning were elderly, or exhibited contraindications for myeloablative conditioning. Neutrophil and platelet engraftment occurred more rapidly in the reduced intensity group (median, 9 days vs. 18 days in the myeloablative group, p<0.0001; median 12 days vs. 22 days in the myeloablative group, p=0.0001, respectively). Acute graft-versus-host disease (> or =grade II) occurred at comparable frequencies in both groups, while the incidence of hepatic veno-occlusive disease was lower in the reduced intensity group (3% vs. 20% in the myeloablative group, p=0.02). The overall 1-yr survival rates of the reduced intensity and myeloablative group patients were 44% and 15%, respectively (p=0.16). The results of present study indicate that patients with advanced hematological malignancies, even the elderly and those with major organ dysfunctions, might benefit from reduced intensity transplantation.
Vidarabine/administration & dosage/*analogs & derivatives ; Treatment Outcome ; Transplantation, Homologous/methods ; Transplantation Conditioning/*methods ; Myeloablative Agonists/*administration & dosage ; Middle Aged ; Male ; International Cooperation ; Humans ; Hematopoietic Stem Cell Transplantation/*methods ; Hematologic Neoplasms/*therapy ; Female ; Busulfan/*administration & dosage ; Aged ; Adult ; Adolescent

OBJECTIVETo investigate the therapeutic effect of conditioning regimen containing fludarabine in nonmyeloablative allogeneic peripheral blood stem cells transplantation (NAST) in the treatment of hematological diseases.

METHODSThirty-six patients with acute leukaemia, severe aplastic anaemia, MDS and myelofibrosis received NAST from HLA matched donors' G-CSF mobilized peripheral blood stem cells after nonmyeloabalative conditioning. The conditioning regimen consisted of CTX, Ara-C, CsA, anti-CD(3) antibody or anti-thymocyte globulin and with or without fludarabine. GVHD prophylaxis was performed with cyclosporine combined methotrexate (no MMF group, n = 5) or mycophenolate mofetil (MMF group, n = 31).

RESULTSAll of the treatment was generally well tolerated and all cases achieved engrafted of the donor cells. In fludarabine group, engraftment was observed in 87.5% (14/16) patients with complete donor chimerism, graft failure was 12.5% (2/16) and in no fludarabine group, 80% (16/20) and 20% (4/20), respectively. The incidence of acute GVHD (grade I - IV) was 27.8% (10/36) and chronic GVHD 22.2% (8/36). In fludarabine group, grade I - II aGVHD was 37.5%, in no fludarabine group, 20%. cGVHD was 12.5% in fludarabine group and in no fludarabine group 30%, respectively. Interstitial pneumonia (IP) was observed in 16.7% (6/36) of the patients, being 18.7% (3/16) and 15% (3/20) in fludarabine and no fludarabine group, respectively. Overall survival rate was 80.5% (29/36) with a median follow-up of 13 months.

CONCLUSIONSThere was no significant difference between fludarabine based (n = 16) and non-fludarabine based conditioning regimen (n = 20) in NAST for the treatment of hematological diseases, regarding for incidence of GVHD, IP, engraftment and survival.

Adolescent ; Adult ; Female ; Follow-Up Studies ; Hematologic Diseases ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Myeloablative Agonists ; administration & dosage ; Transplantation Conditioning ; methods ; Transplantation, Homologous ; Treatment Outcome ; Vidarabine ; administration & dosage ; analogs & derivatives

OBJECTIVETo explore the efficiency and toxicity of non-myeloablative stem cell transplantation (NAST) for hematological disease.

METHODSSeventeen patients, including 3 acute myeloid leukemia, 6 chronic myelogenous leukemia, 4 severe aplastic anemia, 2 non-Hodgkin's lymphoma, 1 multiple myeloma and 1 myelodysplastic syndromes received NAST from HLA-identical sibling donors. Peripheral blood stem cells were mobilized by G-CSF 300 microg/12 hours x 5 d. (2.15 -10.01) x 10(6) CD(34)(+) cells/kg were transplanted. A non-myeloablative conditioning regimen included fludarabine 30 mg.m(-2).d(-1) x 6 d;busulfan 4 mg.kg(-1).d(-1) x 2 d or cyclophosphamide 50 mg.kg(-1).d(-1) x 2 d and antilymphocytic globulin 12 approximately 15 mg.kg(-1).d(-1) x 4 d. Cyclosporin A was used to prevent graft versus host disease (GVHD) alone and no G-CSF was administered after NAST.

RESULTHematopoiesis reconstitution resumed on day 8 to day 19 (average of day 13). Severe mucositis was absent. Hepatic venoocclusive disease did not occur. Infectious complications were rare. Acute and chronic GVHD each occurred in 5 patients. Idiopathic pneumonia was developed in 5 patients. In the follow-up duration of 120 to 425 days, 16 of the 17 cases had a stable mixed or complete chimerical states. Fourteen of 17 patients are alive.

CONCLUSIONNAST is an effective therapy in the treatment of hematological diseases with less complications, less blood transfusion and lower cost.

Adult ; Female ; Follow-Up Studies ; Hematologic Diseases ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Male ; Middle Aged ; Myeloablative Agonists ; administration & dosage ; Transplantation Conditioning ; adverse effects ; methods ; Transplantation, Homologous ; Treatment Outcome ; Vidarabine ; administration & dosage ; analogs & derivatives

BACKGROUND: To compare the mobilizing effects and toxicities of two different doses of cyclophosphamide (CY) plus lenograstim (glycosylated G-CSF), we performed a prospective randomized study by enrolling patients suffering with either high-risk Non-Hodgkin's lymphoma (NHL) or breast cancer undergoing ablative chemotherapy. METHODS: The NHL patients received 4 cycles of CHOP and the breast cancer patients received 2-3 cycles of FAC (FEC) adjuvant chemotherapy. Then, the patients were randomly allocated to receive CY 4 g/m2 (arm A) or 1.5 g/m2 (arm B) in combination with lenograstim. Large volume leukapheresis was carried out and it was continued daily until the target cell dose of 2x10 (6) CD34+ cell/kg was reached. RESULTS: Twenty-seven patients were enrolled in the study. The median number of leukaphereis sessions actually performed was 2.5 sessions in arm A and 3 sessions in arm B. The target cell dose was obtained with the median number of one leukapheresis session in both arms of the study (p=0.09). The collected number of CD34+ cells in the leukapheresis products was higher in arm A than arm B (22.4 vs. 9.9x10 (6) /kg, respectively, p=0.05). Grade III or IV leukopenia was present in 14/15 patients (94%) in arm A and in 1/12 patients (8%) in arm B (p< 0.0001). Grade III or IV thrombocytopenia was present in 8/15 patients (54%) in arm A, but this was not present in any patients of arm B (p=0.0004). Neutropenic fever occurred in 6/15 patients (40%) in arm A, and in 1/12 patients (8%) in arm B (p=0.09). The hematological recovery of the leukocytes and platelets after transplantation was not statistically different between the two doses. CONCLUSION: Low-dose CY plus lenograstim is a safe and effective mobilizing regimen.
Transplantation Conditioning ; Stem Cells/*drug effects ; Recombinant Proteins/administration & dosage/pharmacology ; Prospective Studies ; Myeloablative Agonists/*administration & dosage/pharmacology ; Middle Aged ; Male ; Lymphoma, Non-Hodgkin/*drug therapy ; Leukapheresis ; Humans ; *Hematopoietic Stem Cell Mobilization ; Granulocyte Colony-Stimulating Factor/*administration & dosage/pharmacology ; Female ; Drug Therapy, Combination ; Cyclophosphamide/*administration & dosage/pharmacology ; Chemotherapy, Adjuvant ; Breast Neoplasms/*drug therapy ; Adult