Acute Lymphoblastic Leukemia (ALL) Guidelines 

Updated: Sep 23, 2016
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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National Comprehensive Cancer Network Guidelines

The National Comprehensive Cancer Network (NCCN) provides frequently updated recommendations for the diagnosis and management of acute lymphoblastic leukemia (ALL), along with surveillance milestones or algorithms to monitor response to treatment. The guidelines are further delineated to address differences in the management of adolescent and young adults (AYA), ages 15 to 39 years, from adults 40 years and older. However, the guidelines caution that regardless of chronological age, patients need to be evaluated individually to determine fitness for treatment. [1]

In 2016, the European Society for Medical Oncology (ESMO) released updated guidelines for the management of ALL. [2]

Diagnosis and Risk Stratification

NCCN guidelines note that diagnosis of ALL generally requires the following [1] :

  • Demonstration of ≥ 20% bone marrow lymphoblasts
  • Morphologic assessment of Wright/Giemsa–stained bone marrow aspirate smears
  • Hematoxylin and eosin (H&E)–stained bone marrow core biopsy and clot sections
  • Comprehensive flow cytometric immunophenotyping

For optimal risk stratification and treatment planning in patients with ALL, the NCCN advises that bone marrow or peripheral blood lymphoblasts must be tested for specific recurrent genetic abnormalities, as follows [1] :

  • Cytogenetics – Karyotyping of G-banded metaphase chromosomes
  • Interphase fluorescence in situ hybridization (FISH)
  • Reverse transcriptase polymerase chain reaction (RT-PCR) for fusion genes (eg, BCR-ABL)

The ESMO recommendations concur with those of NCCN while noting that the initial diagnostic work-up should be completed quickly and before any chemotherapy is administered in order to [2] :

  • confirm diagnosis and shorten time to onset of treatment
  • distinguish B-cell precursor (BCP) ALL from T-cell ALL (T-ALL)
  • distinguish Burkitt leukaemia (B-ALL) from BCP-ALL 
  • distinguish Philadelphia (Ph) chromosome-positive (Ph+) ALL from Ph-negative (Ph−) ALL 

As a general rule, the NCCN recommends enrolling patients with ALL in a clinical trial, if possible. Otherwise, NCCN recommendations for first-line treatment are based on risk stratification and age, as follows [1]

  • Philadelphia chromosome–positive (Ph+) ALL (in AYA): Chemotherapy and tyrosine kinase inhibitor (TKI), followed by allogeneic stem cell transplantation (SCT) if an appropriate donor is available; if transplantation is not feasible, continue multiagent chemotherapy and a TKI
  • Ph+ ALL (Adults < 65 y): Chemotherapy and tyrosine kinase inhibitor (TKI); consider allogeneic SCT if an appropriate donor is available and the patient has good performance status and no or limited comorbidities; if transplantation is not feasible, continue multiagent chemotherapy and a TKI
  • Ph+ ALL (Adult ≥ 65 y or with substantial comorbidities): TKI and corticosteroids or TKI and chemotherapy (evaluate end-organ reserve, end-organ dysfunction, and performance status)
  • Ph- ALL (AYA): Pediatric-style multiagent chemotherapy
  • Ph- ALL (Adults < 65 y): Multiagent chemotherapy
  • Ph- ALL (Adults ≥ 65 or with substantial comorbidities): Multiagent chemotherapy or corticosteroids (evaluate end-organ reserve, end-organ dysfunction)

NCCN strongly recommends central nervous system (CNS) prophylaxis for all ALL treatment groups.

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Hematopoietic Stem Cell Transplantation

In 2012, the American Society for Blood and Marrow Transplantation (ASBMT) updated its treatment recommendations for hematopoietic stem cell transplantation (SCT) in adults with acute lymphocytic leukemia (ALL), based on new evidence.

The updated recommendations include the following [3] :

  • Myeloblative allogeneic SCT is an appropriate treatment for adults younger than 35 years, in all risk groups during the first complete remission
  • Allogeneic SCT is recommended over chemotherapy for all adults with ALL during the second or subsequent complete remission
  • Allogeneic SCT is preferred over autologous SCT, with similar outcomes for related and unrelated allogeneic SCT
  • Imatinib therapy before and/or after SCT for Ph+ ALL results in higher survival rates

The 2016 ESMO guidelines inclue the following recommendations [2] :

  • AutoSCT is not recommended outside of clinical trials
  • Allogeneic SCT is recommended after first complete remission in all patients with poor minimal residual disease, but not recommended for standard risk patients with a sustained molecular response
  • After the second complete remission, allogeneic SCT was found superior to non-transplantation
  • Cord blood transplantation may be considered if no HLA-well-matched donor is found or if there is need for urgent need of SCT
  • Total body irradiation regimens are recommended for myeloablative SCT; reduced-intencity conditioning regimens should only be utilized for adults in remission unfit for myeloablative conditioning and elderly fit patients
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