0000000000246691
AUTHOR
Gerhard Heil
Salvage Therapy of Adult ALL
In a first study (1986 to 1992) the German Relapsing ALL Study Group (GRALLSG) has treated 67 adult patients with a first relapse of ALL. A first phase of induction consisted of vindesine, daunorubicin, asparaginase, and prednisone, a second phase of high-dose cytosine-arabinoside (Hd ara-C) and VP16. Results: 45 CR, 2 PR, 13 failures, 7 early death. 25 patients received a BMT. 10 had an allogeneic BMT in CR, 5 after another relapse or with refractory disease. Of 10 with autologous BMT 8 have been in 2nd CR. Only 4 of all 67 patients are surviving without relapse: One after unrelated BMT (36+mo), two after autologous BMT in 2nd CR (46+, 64+mo), and one after chemotherapy (61+mo). One patien…
Induction Therapy with Idarubicin, Ara-C, and VP-16, Followed by G-CSF and Maintenance Immunotherapy with Interleukin-2 for High-Risk AML
Aggressive chemotherapy followed by administration of G-CSF and maintenance therapy with interleukin-2 was evaluated in 16 patients with advanced myelodxysplastic syndrome, 47 patients with AML evolving from myelodysplastic syndromes, 3 patients with subacute myeloid leukemia and 5 patients with secondary AML. Median age was 59 years (range: 23 to 76 years). All patients achieving a complete remission (CR) after two induction courses went on to receive two consolidation courses, to be followed by randomization to either high-dose or low-dose IL-2 to evaluate the potential of IL-2 to eliminate residual leukemic cells and to prolong the duration of CR. Patients ≤ age 55 with an HLA identical …
Chemotherapy with Idarubicin, Ara-C,VP-16, Amsacrine, Followed by G-CSF and Maintenance Immunotherapy with Interleukin-2 for Patients with High-Risk Acute Myeloid leukemia: a 3-Years Follow-Up
To improve the complete remission (CR) rate and to prolong CR duration in patients with advanced MDS, AML evolving from MDS, and secondary AML, a phase-III trial of aggressive chemotherapy followed by G-CSF was initiated in January 1992. Pts. achieving a CR were randomized to receive either high-dose or low-dose IL-2 to evaluate the potential of this cytokine to eliminate residual leukemic cells and to prolong the CR duration.
GM-CSF in a Double-Blind Randomized Placebo-Controlled Trial in Therapy of Adult Patients with De Novo Acute Myeloid Leukemia
Despite the fact that 60%–70% of patients with de novo acute myeloblastic leukemia (AML) achieve a complete remission (CR) of the disease only about 20%–30% of the patients remain in long term remission and are probably cured [1,2]. These rather disappointing long-term results argue in favor of an even more intensive induction and post-remission therapy. This intention is, however, at time limited by therapy associated toxicity. Especially haematotoxicity seems to be the limiting factor in that patients with profound neutropenia are at high risk of developing fatal infectious complications [3]. In this context haematopoietic growth factors, such as granulocyte-macrophage colony-stimulating …
Granulocyte–Macrophage Colony-Stimulating Factor in the Therapy of Adults with De Novo Acute Myeloblastic Leukemia: An Update of a Double-Blind Randomized, Placebo-Controlled Trial
We investigated whether granulocytemacrophage colony-stimulating factor (GMCSF) given concomitantly with chemotherapy (CT) improves the outcome of adults with de novo acute myeloblastic leukemia (AML) by increasing the efficacy of CT and reducing infections. CT included cytarabine (ara-C) daunorubicin, and etoposide (DAV) for induction and early consolidation therapy and one cycle with high-dose (patients aged ≤50 years) or intermediate-dose ara-C (patients aged >50 years) /daunorubicin for late consolidation therapy. Eighty patients were randomized after DAV 1 to receive either GM-CSF (Escherichia coli, 250 µg/m2 per day, s.c.) or placebo starting 48 h prior to DAV II and the subsequent co…
Impact of Age and Midostaurin-Dose on Response and Outcome in Acute Myeloid Leukemia with FLT3-ITD: Interim-Analyses of the AMLSG 16-10 Trial
Abstract Background: Internal tandem duplications (ITD) in the receptor tyrosine kinase FLT3 occur in roughly 25% of younger adult patients (pts) with acute myeloid leukemia (AML). The multi-targeted kinase inhibitor midostaurin combined with intensive chemotherapy has shown activity against AML with FLT3 mutations. However, toxicity and potential drug-drug interactions with strong CYP3A4 inhibitors such as posaconazole may necessitate dose reduction. Aims: To evaluate the impact of age and midostaurin dose-adaptation after intensive induction chemotherapy on response and outcome in AML with FLT3-ITD within the AMLSG 16-10 trial (NCT01477606). Methods: The study included adult pts (age 18-7…
Aggressive chemotherapy combined with G-CSF and maintenance therapy with interleukin-2 for patients with advanced myelodysplastic syndrome, subacute or secondary acute myeloid leukemia--initial results.
Aggressive chemotherapy of advanced myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) evolving from MDS, subacute AML and secondary AML has usually been associated with low complete remission (CR) rates, a high incidence of early death, and low disease-free survival. We therefore have initiated a phase-III trial of aggressive chemotherapy consisting of idarubicin, cytosine arabinoside, and VP-16 to improve the CR rate. Each chemotherapy cycle is followed by G-CSF to accelerate neutrophil recovery and to reduce the incidence of infections. Until now, 19 patients with high-risk AML have been entered. The CR rate is 47%, with only one death during induction. Patients achieving CR ar…
Condensed Versus Standard Schedule of High-Dose Cytarabine Consolidation Therapy with Pegfilgrastim Growth Factor Support in Acute Myeloid Leukemia
Abstract Background: The concept of intensive post-remission chemotherapy in acute myeloid leukemia (AML) is based on the observation that despite achievement of a first complete remission (CR) after intensive induction therapy virtually all patients relapse in the absence of further treatment. Moreover, randomized studies showed that intensive post-remission consolidation chemotherapy was superior to prolonged low-dose maintenance therapy in younger patients. With regard to consolidation therapy, the landmark study conducted by the Cancer and Leukemia Group B established the current standard for patients aged 60 years and younger with high-dose cytarabine (HDAC) 3g/m² bidaily on days days …
Intensive chemotherapy with idarubicin, ara-C, etoposide, and m-AMSA followed by immunotherapy with interleukin-2 for myelodysplastic syndromes and high-risk Acute Myeloid Leukemia (AML)
Intensive chemotherapy followed by treatment with interleukin-2 (IL-2) was evaluated in a prospective, randomized, multicenter trial including 18 patients with refractory anemia with excess of blasts in transformation (RAEB-T), 86 patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndromes, and six patients with secondary AML after previous chemotherapy. Median age was 58 years (range: 18-76 years). Forty-nine patients (45%) achieved a complete remission (CR) after two induction cycles with idarubicin, ara-C, and etoposide, 52% of them aged/=60 years and 35% aged60 years (p=0.06). After two consolidation courses, patients were randomized to four cycles of either high-…