Autologous stem cell transplantation after complete remission and first consolidation in acute myeloid leukemia patients aged 61-70 years: results of the prospective EORTC-GIMEMA AML-13 study.

BACKGROUND AND OBJECTIVES: The optimal post-remission treatment for elderly patients with acute myeloid leukemia (AML) is presently unknown. Recent studies have reported the feasibility of autologous peripheral blood stem cell transplantation (PBSCT) in this population. We evaluate the outcome of this post-remission approach after complete remission (CR) and consolidation in elderly patients included in the EORTC-GIMEMA AML-13 trial. DESIGN AND METHODS: PBSCT after induction and consolidation chemotherapy was evaluated in patients aged 61 to 70 years with a WHO performance status 0-1. The induction therapy was mitoxantrone, etoposide and cytarabine (MICE) with or without granulocyte colony-stimulating factor (G-CSF) during and/or after chemotherapy. The consolidation therapy consisted of non-infusion or infusional idarubicin, etposide and cytarabine (mini-ICE). RESULTS: Sixty-one patients were scheduled for stem cell harvest by leukapheresis after s.c. recombinant human G-CSF administration initiated after hematopoietic recovery from consolidation. Stem cells were effectively harvested from 54 patients. A median of two aphereses (range, 1-5) were performed, resulting in a median collection of 11.7 x 10(8) nucleated cells/kg (range, 2.4-99.8) containing 40.2 x 10(4) CFU-GM/kg (range, 0-786.8), and 5 x 10(6) CD34+ cells/kg (range, 0.1-99.8). For the whole group of 61 patients, the median disease-free survival (DFS) was 1.0 years and the 3-year DFS rate was 21%, while the median overall survival (OS) was 1.4 years and the 3-year OS rate was 32%. A total of 26 patients could not be autografed due to inadequate/no harvest (21 patients), early relapse (3 patients), or treatment refusal (2 patients). Autologous transplantation was performed in 35 patients following conditioning with the BAVC regimen. The median time for granulocyte recovery >0.5 109 yen/L was 24 days and for platelets >20 x10(9)/L was 23 days following transplantation. After a median follow-up of 5.0 years from transplantation, the median DFS and OS were 1.1 and 1.6 years respectively, and the 3-year rates were 28% and 39% respectively. Eight autografted patients were still in continuous complete remission, 22 patients had relapsed and five had died in CR. INTERPRETATION AND CONCLUSIONS: Intensification of remission including autologous PBSCT is feasible in about half of harvested patients aged 61 to 70 years old, and did not improve the general outcome. This shows the limitations of autologous PBSCT and other intensive treatment modalities in elderly AML patients. Key words: acute myeloid leukemia, elderly, autologous stem cell transplantation.

Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study.

The role of glycosylated recombinant human granulocyte colony-stimulating factor (G-CSF) in the induction treatment of older adults with acute myeloid leukemia (AML) is still uncertain. In this trial, a total of 722 patients with newly diagnosed AML, median age 68 years, were randomized into 4 treatment arms: (A) no G-CSF; (B) G-CSF during chemotherapy; (C) G-CSF after chemotherapy until day 28 or recovery of polymorphonuclear leukocytes; and (D) G-CSF during and after chemotherapy. The complete remission (CR) rate was 48.9% in group A, 52.2% in group B, 48.3% in group C, and 64.4% in group D. Analysis according to the 2 x 2 factorial design indicated that the CR rate was significantly higher in patients who received G-CSF during chemotherapy (58.3% for groups B + D vs 48.6% for groups A + C; P = .009), whereas no significant difference was observed between groups A + B and C + D (50.6% vs 56.4%, P = .12). In terms of overall survival, no significant differences were observed between the various groups. Patients who received G-CSF after chemotherapy had a shorter time to neutrophil recovery (median, 20 vs 25 days; P < .001) and a shorter hospitalization (mean, 27.2 vs 29.7 days; P < .001). We conclude that although priming with G-CSF can improve the CR rate, the use of G-CSF during and/or after chemotherapy has no effect on the long-term outcome of AML in older patients.

Calprotectina epidérmica en la reacción injerto-versus-huésped con depleción linfocitaria cutánea / Epidermal calprotectin in lymphocyte-depleted cutaneous graft-vs-host reaction

Una de las complicaciones más importantes asociada a los trasplantes de médula ósea es la Reacción Injerto versus Huésped (RIVH). Los regímenes inmunosupresores reducen la severidad de las lesiones cutáneas determinando una forma peculiar de RIVH con deplesión linfocitaria (RIVH-DL), caracterizada por pocas células inflamatorias reconocibles y casi una total ausencia de daño epidérmico. Los recientemente actualizados criterios histopatológicos para la RIVH ayudan poco para el diagnóstico de la RIVH-DL. Como la calprotectina (L1-proteína) ha sido encontrada en diversos tipos de estress epitelial, analizamos la calprotectina epitelial en la RIVH-DL. La expresión de calprotectina se estudió por inmunohistoquímica usando Mac 387 moAb en 50 casos de RIVH-DL y 40 casos de reacciones tóxicas secundarias a los regímenes condicionantes pre-trasplante o por drogas post-trasplante. Se detectó calprotectina en queratinocitos de apariencia normal en todos los casos de RIVH-DL y en la mayoría de las dermatitis con citotoxicidad inducidas por drogas. Concluímos que la inmunoreactividad a la calprotectina aparenta ser una clave diagnóstica para la RVIH-DL. Se expresión aparece precozmente en el curso de la RIVH-DL independientemente del grado histológico de la reacción. Sin embargo, no puede ser usada en forma aislada para distinguir entre una RIVH-DL inicial y una dermatitis inducida por drogas

Calprotectina epidérmica en la reacción injerto-versus-huésped con depleción linfocitaria cutánea / Epidermal calprotectin in lymphocyte-depleted cutaneous graft-vs-host reaction

Una de las complicaciones más importantes asociada a los trasplantes de médula ósea es la Reacción Injerto versus Huésped (RIVH). Los regímenes inmunosupresores reducen la severidad de las lesiones cutáneas determinando una forma peculiar de RIVH con deplesión linfocitaria (RIVH-DL), caracterizada por pocas células inflamatorias reconocibles y casi una total ausencia de daño epidérmico. Los recientemente actualizados criterios histopatológicos para la RIVH ayudan poco para el diagnóstico de la RIVH-DL. Como la calprotectina (L1-proteína) ha sido encontrada en diversos tipos de estress epitelial, analizamos la calprotectina epitelial en la RIVH-DL. La expresión de calprotectina se estudió por inmunohistoquímica usando Mac 387 moAb en 50 casos de RIVH-DL y 40 casos de reacciones tóxicas secundarias a los regímenes condicionantes pre-trasplante o por drogas post-trasplante. Se detectó calprotectina en queratinocitos de apariencia normal en todos los casos de RIVH-DL y en la mayoría de las dermatitis con citotoxicidad inducidas por drogas. Concluímos que la inmunoreactividad a la calprotectina aparenta ser una clave diagnóstica para la RVIH-DL. Se expresión aparece precozmente en el curso de la RIVH-DL independientemente del grado histológico de la reacción. Sin embargo, no puede ser usada en forma aislada para distinguir entre una RIVH-DL inicial y una dermatitis inducida por drogas (AU)