Canterbury DHB

Context

Non-trial Patients

In This Section

Philadelphia-negative adult ALL

Philadelphia-positive adult ALL

Induction chemotherapy

Philadelphia-negative adult ALL

Patients aged up to 65 years were eligible for intensive induction chemotherapy in the UKALL12 and 14 trials. An increasing role for allogeneic transplantation has been recognized in selected high risk ALL in first remission. High risk Ph-negative patients include those >35 years, slow responders, or those with a high WCC. Studies often include highly selected patients. Definitions of high risk are variable. The UKALL12 trial attempted a donor versus no donor randomization in all Ph-negative patients with an overall survival benefit shown for standard risk patients (62 v 52% at 5 years). This trial only allowed sibling donors. A meta-analysis of 7 studies did not show a survival advantage for patients NOT high-risk. In the UKALL12 study less than a third of patients with a donor received the intended treatment. This was mainly due to early relapse. For high risk patients, the reduced relapse risk was abrogated by a high non-relapse mortality. The UKALL14 study risk stratified patients based on age, white count, genetics, remission status, donor source to recommend allogeneic transplant or not and this would be explored by the SCT multidisciplinary team for each individual patient of transplantable age. The picture has been further complicated by the possibility of using haploidentical transplants for persons with ALL, an approach which has proved successful in some of our patients. See Srour, S. A., et al. (2017). "Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for High-Risk Acute Lymphoblastic Leukemia." Biology of Blood and Marrow Transplantation 23(2): 318-324.

Philadelphia-positive adult ALL

We strongly recommend you read a recent publication by a leading expert in this field. See Chiaretti, S. and Foà, R. (2015). "Management of adult Ph-positive acute lymphoblastic leukemia." ASH Education Program Book 2015: 406-13.

Patients who are considered fit should be given intensive induction chemotherapy and referred to the transplant committee for consideration of allogeneic transplantation in first complete remission if a well-matched sibling or unrelated donor is available. The addition of imatinib or dasatinib to induction chemotherapy increases the remission rate and reduces the proportion of patients who relapse before transplant. Dasatinib is theoretically more attractive in Ph+ALL as it has a wider spectrum of action and penetrates CNS better. Dasatinib is not funded for patients with ALL.

Older patients may be considered for less intensive induction. Even elderly patients unfit for chemotherapy may obtain a complete remission with steroids and dasatinib alone.

Induction chemotherapy

There is no single best induction regimen. CR rates of 80-90% have been reported in most studies.

Most induction regimes follow the approach derived from successful treatment of paediatric patients of two induction courses incorporating steroids, vincristine, an anthracycline, and asparaginase. Asparaginase has been shown to be an important component of paediatric regimens. In these younger patients receiving intensive therapy it is used as a long acting preparation, PEG asparaginase.

Interestingly, the hyper-CVAD induction regimen proposed by the MD Anderson Cancer Center does not include asparaginase and the results of treatment are similar to other regimens. The ALL5 protocol was based around hyper-CVAD induction. Improved results with hyper-CVAD and with other ALL protocols have been reported by adding monoclonal anti-CD20 antibody (rituximab). See Maury, S.et al. (2016). "Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia." New England Journal of Medicine 375: 1044-53.

The early death rate in all regimens is around 7%. This is mainly due to opportunistic infection, particularly invasive fungal infection.

Useful expert advice on the selection and management of older patients undergoing intensive treatment is included in a recent review. See Gökbuget, N. (2016). "Treatment of older patients with acute lymphoblastic leukemia." ASH Education Program Book 2016: 573-9.

About this Canterbury DHB document (29626):

Document Owner:

Peter Ganly (see Who's Who)

Issue Date:

November 2018

Next Review:

November 2021

Keywords:

Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document. Disclaimer

Topic Code: 29626