Manuel Ayala-Sánchez

Allogeneic bone marrow transplantation for chronic myeloid leukemia: a single center experience.

BACKGROUND Bone marrow transplantation (BMT) is the therapy of choice for patients with chronic myeloid leukemia (CML) who have a human leukocyte antigen (HLA)-identical donor and are under 50 years of age. METHODS Here, 45 patients with CML were treated with busulfan (Bu) 16 mg/kg and cyclophosphamide (Cy) 120 mg/kg before allogeneic BMT from an HLA-identical sibling 27 (60%) or a 1-antigen mismatch donor 18 (40%). Eighteen patients (40%) were in the early chronic phase (CP) and 27 (60%) in late CP. We used cyclosporin-A (CsA) in 20 patients and cyclosporin-A-methotrexate (CsA-MTX) in 25 for graft-vs.-host disease (GVHD) prophylaxis. RESULTS We observed a high incidence of acute and chronic GVHD (69% and 67%, respectively). A multivariate analysis identified differences in the sex of the donor and the recipient (p = 0.03) and grade III-IV acute GVHD (p = 0.0001) as significant adverse influences on disease-free survival. Age, sex, chronic GVHD, disease phase, one antigen-mismatch and use of CsA or CsA-MTX had no statistical significance. The 3-year probabilities of relapse, disease-free survival, and overall survival were 11%, 55%, and 60%, respectively. Transplant-related mortality occurred in 31% of the cases. The high frequency of GVHD is explained by HLA determination by serological typing, differences in sex between the donor and recipient, and a high proportion (40%) of 1 antigen-mismatch donors. CONCLUSIONS BMT is a procedure feasible for patients with CML in early and late chronic phase and even in those with an HLA non-identical donor. Strategies directed to decrease acute GVHD could improve the outcome of these patients.

Prospective randomized clinical trial comparing high-dose ifosfamide + GM-CSF vs high-dose cyclophosphamide + GM-CSF for blood progenitor cell mobilization

Between August 1994 and June 1999, 56 patients were prospectively randomized to receive ifosfamide 10 g/m2 + GM-CSF 5 μg/kg/day (IFO+GM-CSF n = 28) and cyclophosphamide 4 g/m2 + GM-CSF 5 μg/kg/day (CY+GM-CSF n = 28). Both groups were comparable for age, gender, diagnosis, disease stage and previous chemotherapy. The IFO+GM-CSF group demonstrated a shorter median interval between therapy and apheresis (10 days (8–14) vs 13 days (8–25) P = 0.002), median number of doses of GM-CSF (9 (7–13) vs 15 (9–31) P = 0.001), median of days with aplasia (0.5 (0–10) vs 6 (0–21) P = 0.001), median days with fever (0 (0–6) vs 3 (0–9) P = 0.006) and median of days using i.v. antibiotics (0 (0–11) vs 7.5 (0–19) P = 0.002). The median MNC yield was similar in both groups. The CD34+ cell yield was better in the CY+GM-CSF group (3.14 (0.9–11.8) vs 5.33 (0.08–32)) but not at significant levels (P = 0.1). White blood cell hematopoietic recovery was more rapid in the CY+GM-CSF group (16 (10–22) vs13 (10–24) P = 0.02). Platelet engraftment was similar in both groups. Costs of mobilization and transplantation were almost the same:

Clinical relevance of NK, NKT, and dendritic cell dose in patients receiving G-CSF-mobilized peripheral blood allogeneic stem cell transplantation

28 570 (

Intravesical rhGM-CSF for the treatment of late onset hemorrhagic cystitis after bone marrow transplant.

18 527–

CDKIs p18(INK4c) and p57(Kip2) are involved in quiescence of CML leukemic stem cells after treatment with TKI.

47 028) and

Casiopeina III-Ea, a copper-containing small molecule, inhibits the in vitro growth of primitive hematopoietic cells from chronic myeloid leukemia

30 020 (

Global gene expression profiles of hematopoietic stem and progenitor cells from patients with chronic myeloid leukemia: the effect of in vitro culture with or without imatinib

17 281–

Malignant fibrous histiocytoma after allogeneic bone marrow transplantation.

67 591), respectively (P = 0.9). There were no differences in disease-free survival and overall survival between both groups. Mild and transient non-hematological toxicity (hemorrhagic cystitis, decrease in serum creatinine clearance and CNS dysfunction) was seen most frequently in the IFO+GM-CSF group. Bone Marrow Transplantation (2000) 25, 1141–1146.

Parthenolide and DMAPT induce cell death in primitive CML cells through reactive oxygen species

To analyze the relationship between the cellular composition of peripheral blood allografts and clinical outcome, we performed a prospective study in 45 adult patients who underwent allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT) from a histocompatibility leukocyte antigen identical sibling donor for different hematological malignancies. The dose of CD34+, CD3+, CD4+, CD8+, and CD19+ lymphocytes, natural killer (NK) cells, natural killer T (NKT) cells, type 1 and type 2 dendritic cells (DC1 and DC2), as well as regulatory T (Treg) lymphocytes was analyzed. All patients were conditioned with busulphan and cyclophosphamide (BuCy2) ± VP-16 and received a short course of methotrexate and cyclosporin-A as graft-versus-host disease (GVHD) prophylaxis. Acute GVHD (aGVHD) was present in 9 of 43 (21%) patients, and chronic GVHD (cGVHD) developed in 18 of 39 (46%) patients. There was a significantly higher incidence of aGVHD in patients receiving more than 6×106/kg CD34+ cells. In univariate analysis, variables associated with better survival were as follows: a dose of less than 1.5×107/kg NKT cells and less than 1.7×106/kg DC2 for disease-free survival (DFS), and a dose of less than 3×107/kg NK cells, less than 1.5×107/kg NKT cells, less than 3×106/kg DC1, and less than 1.7×106/kg DC2 for overall survival (OS). In the Cox regression analysis, the dose of NKT cells was the only variable associated with better DFS, while the doses of NK, NKT, and CD34+ cells (less than 8×106/kg) were associated with better OS. In conclusion, different circulating cell populations, other than CD34+ cells, are also of relevance in predicting the clinical outcome after allogeneic peripheral blood HSCT.

Intermediate doses of melphalan and dexamethasone are better than vincristine, adriamycin, and dexamethasone (VAD) and polychemotherapy for the treatment of primary plasma cell leukemia.

In the present study, we assessed the clinical effect of recombinant human granulocyte–macrophage colony-stimulating factor (rhGM-CSF) in the treatment of refractory, grade III–IV hemorrhagic cystitis (HC) in six patients who underwent bone marrow transplantation (BMT). These were four males and two females, aged 24–40 years (median age 30.5 years). All received allogeneic BMT from HLA-identical siblings after preparation with busulfan–cyclophosphamide. HC was evident 24.5 days (range 15–33 days) after BMT. Median duration of HC before treatment was 5 days (range 4–9 days). Treatment consisted of intravesical instillation of rhGM-CSF (400 μg) for 3 consecutive days. A complete response was observed in three patients, the other three showed a partial response. Median time to achieve response was 36 h (range 0.2–72 h). Hematuria was controlled after the first (two patients), second (two patients) or third (two patients) dose of intravesical rhGM-CSF. Patients were discharged from the hospital 10.5 days (range 3–41 days) after treatment. All patients have been followed for up to 10 months and none have required further treatment. No systemic or bladder side-effects have been observed. Although our results indicate that intravesical instillation of rhGM-CSF is effective in the treatment of HC, a phase II clinical trial, including a larger series of patients, is needed.