New transplantation strategies and post-transplant treatment options for ALL patients from an international perspective

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still the only curable method for high-risk acute lymphoblastic leukemia (ALL) patients, including intermediate-risk ALL patients who have not achieved/cannot maintain minimal residual disease (MRD) negative complete remission
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In the past ten years, allo-HSCT has developed rapidly, and most patients can be matched to a suitable donor for smooth transplantation through unrelated donors, haploid donors and umbilical cord blood
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The accessibility of donors is generally improved, which meets the needs of patients who need allo-HSCT, but the pursuit of the best transplant strategy and maintenance treatment options after transplantation to maintain long-term disease-free survival (DFS) with minimal therapeutic toxicity still needs to be explored
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Professor Aaron C.
Logan from the University of California, San Francisco explained and shared the new transplantation strategies and post-transplant treatment options for ALL patients.
The editor summarizes the main contents as follows
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Who needs transplantation? When is the best time to transplant? The population of ALL patients suitable for allo-HSCT is constantly changing.
Patients who were previously considered to be in need of transplantation can now choose non-transplantation treatments, such as the first-line treatment of hyper-CVAD combined with ponatinib for Ph+ B-ALL patients
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If patients with Ph-ALL recognize recurrence predictors, such as Ph-like kinase translocations and mutations, early in treatment, these patients can benefit from transplantation as soon as possible
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For ALL patients with intermediate-risk genetic cytological changes, allo-HSCT or continued chemotherapy can be selected based on the MRD status after induction chemotherapy.
Different chemotherapy regimens continue for 2 or 3 cycles
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However, there is always a question in this seemingly standardized diagnosis and treatment plan: Do all patients who reach MRD negative need allo-HSCT? Does MRD negative mean different prognosis in patients with different genotypes of ALL? Due to the lack of conclusive data to guide decision-making, these issues are currently hypothetical
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MRD-negative high-risk patients with cytogenetic changes need to undergo allo-HSCT as soon as possible, while low-risk patients may not choose allo-HSCT
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Regardless of the prognosis risk, MRD-positive patients have a very high risk of recurrence, and it is best to perform allo-HSCT as soon as possible after induction chemotherapy has achieved complete remission
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Strategies for optimizing the prognosis of allo-HSCT in ALL patients.
Selecting ALL patients suitable for allo-HSCT needs to find the most suitable donor to minimize the incidence of graft-versus-host disease (GVHD) and prolong the GVHD-free survival period (GRFS)
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Belintolumab can be used for patients whose MRD continues to be positive after 2-3 cycles of chemotherapy, and can convert about 80% of patients to MRD-negative.
It is a very good choice for this part of patients, which can make more The patient undergoes allo-HSCT
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However, in addition to this evidence-based medicine-based allo-HSCT pre-intervention, doctors also need to consider several other decisive factors, including donor source, pretreatment plan, GVHD prevention plan, post-transplant immunosuppression and maintenance treatment plan, etc.
These factors may affect the long-term prognosis of patients
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At present, the "best" donor type for adult ALL remains to be clarified, and this is difficult to verify with randomized clinical trials, because almost no patient can obtain all types of donors at the same time
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In recent years, great progress has been made in alternative donors.
For example, the prognosis of transplantation using haploid-matched donors has improved with the optimized use of cyclophosphamide.
Patients receiving haploid transplantation seem to be related to traditional unrelated donors.
Patients with sibling donors have similar prognosis
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The new research results show that the intensity of pretreatment is closely related to the type of donor.
Compared with lightly pretreated haploidentical donors, matching irrelevant donors are more suitable for use, but it is still necessary to match the donor and haploidentical donors.
Contrast test to confirm
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Umbilical cord blood (UCB) is less clinically used than other donors, but some patients are very suitable for UCB transplantation
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In some UCB transplant centers, the outcome of UCB transplantation for ALL may be better than other donor types
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The standard procedure before allo-HSCT for ALL patients usually includes systemic radiotherapy (TBI).
The main goal is to eliminate all leukemia cells.
In addition, belintoxumab treatment is also important because the drug may prevent extramedullary recurrence
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Non-TBI treatment options such as clofarabine/busulfan are also optional, and there is no randomized controlled study with TBI
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Allo-HSCT is an effective method for the treatment of high-risk and relapsed and refractory ALL.
Therefore, post-transplant efficacy evaluation and maintenance treatment are essential.
These maintenance treatment options require prolonging the patient’s DFS and do not Bring more drug treatment toxicity
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The use of tyrosine kinase inhibitors for Ph+ ALL patients after transplantation can increase the DFS rate, but for Ph-ALL patients, there is no clear plan to prevent recurrence after transplantation
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Except for the gradual reduction of immunosuppression, donor lymphocyte infusion, and belintolumab, there are few treatment options to reduce the recurrence rate after transplantation
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Preliminary data show that it is feasible to use belintoomab for maintenance therapy after allo-HSCT, but it still cannot completely overcome the problem of re-emergence of MRD positive after HSCT
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MRD quantitative monitoring using second-generation sequencing technology (such as the FDA-approved ClonoSEQ test) has high sensitivity, can identify patients at risk of recurrence, and allow enough time for these patients to implement preemptive intervention treatment, but this type of treatment plan is still Limited
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Discussion ALL is a malignant tumor that chooses a treatment plan based on the MRD status.
Transplantation when the MRD is negative can obtain a better treatment outcome.
It is still difficult to accurately distinguish this type of patient group
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If patients achieve MRD-negative complete remission in the early stage of drug treatment, these patients are the biggest beneficiaries of allo-HSCT after the first remission
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The challenge in this field is to develop better methods to identify ALL patients who must undergo allo-HSCT, while also striving to pursue longer DFS in high-risk patients undergoing transplantation
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Therefore, it is important to further explore high-sensitivity MRD monitoring methods, identify patients at risk of recurrence earlier, and choose more effective MRD clearance strategies
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At the same time, in these patients who do not need allo-HSCT, these methods and strategies can also be used to identify patients at risk of recurrence, and timely meaningful interventions
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Reference source: Aaron C.
Logan.
2021 SOHO.
EXABS-104-ALL.
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