•The risk of fungal infection is high, especially during long periods of neutropenia or aplasia

•Lymphocytopenia may result in opportunistic infections

3.6Therapy

•Before 1970, nearly all children with AML died. Since then cooperative study protocols with different cytotoxic drug combinations have led to long-term remission in approximately 50–60% of children (see also table Prognostic factors in AML)

•Allogeneic hematopoietic stem cell transplantation (HSCT) has been reported in multiple studies to improve disease-free survival but not always overall survival because of treatment-related mortality. There appears to be no advantage of HSCT in first remission for patients with favorable risk AML although there may be a survival advantage for patients with intermediate-risk AML. It is unclear whether HSCT improves survival in patients with high-risk AML, although most of these patients do undergo transplantation

•There is no evidence that autologous HSCT improves survival in patients with AML

•CNS prophylaxis includes either intrathecal cytarabine (ARAC) or cytarabine in combination with methotrexate and prednisone, often in parallel with systematic high-dose cytarabine treatment. Of note, intrathecal ARAC should not be given concurrently with high-dose, systemic ARAC as the combination can result in severe transverse myelitis and paralysis. There are not definitive data that cranial radiation provides better outcomes than intrathecal CNS leukemia prophylaxis. The incidence of CNS relapse is decreased to less than 5% in patients treated with intrathecal and systemic chemotherapy

•Certain subtypes of AML are still associated with a poor prognosis (for instance AML with monosomy seven or secondary AML)

3.6.1Induction Therapy

•Cytarabine (e.g., ara-C) and anthracyclines (e.g., daunorubicin or liposomal daunorubicin L-DNR (reduction of cardio-toxicity) and 2-Chloro-2-deoxyadenosine (C-CDA, higher rate of remission) lead to approximately 70% remission (less than 5% blasts in bone marrow) within 4–6 weeks and no other evidence of leukemias

•Other combinations, such as 6-thioguanine or etoposide in combination with daunorubicin or other anthracyclines, such as idarubicin or mitoxantrone, result in remissions up to 85%

•Supportive therapy and prophylaxis (antibacterial, antiviral, antifungal) and the use of hematopoietic growth factors reduce morbidity and lethality. Granulocyte colonystimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF) shorten the periods of neutropenia, and diminish the frequency of infections and days of hospitalization, but do not influence the rate of remission or overall outcome.

3.6.2Remission and Postremission Therapy

•Consolidation and intensification therapy over the course of approximately 6–12 months results in an overall survival between 50% and 55%. Some treatment programs use maintenance therapy, although this approach has not proven to be of benefit in multiple other studies when intensive chemotherapy is used

MRD detection at the end of induction or in the postremission setting is associ-

ated with a poor prognosis (see Chap. 1, page 9).

3.6.3Allogeneic Hematopoietic Stem Cell Transplantation

•The possibility of an antileukemic effect of the donor immune system (graft vs leukemia or GVL), together with supportive therapy and prophylaxis against graft-versus-host disease (GVHD), results in an improved outcome for certain subtypes of AML (see discussion above)

•A GVL effect is less effective in transplantation between identical twins or after extensive T-cell depletion of the donor stem cells

•Adverse late sequelae after transplantation include chronic GVHD, growth retardation, sterility, and the risk of secondary malignancy

•The frequency of leukemia-free survival after transplantation is 50–70%

In the absence of an HLA matched, family donor, matched or mismatched unre-

lated bone marrow or cord blood donors may be used; in some instances, related haploidentical donor transplantation may be considered. All of these types of transplantation should be ideally carried out on a clinical trial as they are still experimental.

3.6.4Autologous Hematopoietic Stem Cell Transplantation

•Studies have shown equivalent survival to postremission chemotherapy. There is no evidence for autologous stem cell transplantation

Prognostic factors in AML (for further details see reference below)