Non-trial Patients

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

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. Asparaginase has a unique combination of toxicities, see Aldoss, I. and D. Douer (2020). "How I treat the toxicities of pegasparaginase in adults with acute lymphoblastic leukemia." Blood 135(13): 987-995.

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 this 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)
Last Reviewed:	December 2021
Next Review:	December 2024
Keywords:
Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document. Disclaimer The Haematology Department Protocols and Guidelines (the Red Book) are intended as a guide for registered health professionals to communicate guidelines and share best practices with supporting health professionals within New Zealand district health boards. They are not intended to be provided to or used as a reference for patients or non-registered health professionals. All health professionals must exercise their own clinical judgement and use pertinent clinical data when treating patients. The authors and editors of this publication have checked with sources believed to be reliable in their effort to provide information that is complete and in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical science, neither the authors, editors, publisher, nor any other party who has been involved in preparing or publishing this work warrants that the information contained in it is accurate or complete in every respect. They therefore have no liability (whether in tort (including negligence) or otherwise) for any loss or damage arising out of any reliance on this information. This publication has been compiled by the staff and contractors of Canterbury District Health Board (CDHB) and as such CDHB has copyright for this book. Amendments must be authorised in accordance with the documented process. No release of part of, or all of, this publication to any other party or organisation is permissible without the prior approval of the designated document owner.
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