Transplantation of allogeneic stem cells for chronic myeloid leukemia

       (1) Indications Since imatinib was applied to the treatment of CML at the end of last century, TKI has gradually replaced allo-HSCT as the first-line regimen for CML treatment. However, as the only curable treatment option for CML at present, allo-HSCT is still widely used in the treatment of CML. Especially in China, as in other Asian countries, the age of onset of CML is significantly lower than in Western countries, and younger patients have a higher demand for a cure of the disease. In the era of TKI therapy, the patient’s disease status should be accurately evaluated, the risk and survival benefit of TKI and allo-HSCT therapy for the patient should be fully considered, and the treatment plan should be selected in combination with the patient’s treatment wishes. Sun Zhiqiang, Department of Hematology, Affiliated Hospital of Guizhou Medical University, can refer to the following principles for the screening of patients with allo-HSCT: 1) newly diagnosed pediatric and young patients with CML; 2) patients in the chronic stage, if the Sokal score is high risk and the transplant EBMT risk score is ≤2, and there is an HLA-compatible donor, first-line allo-HSCT therapy can be selected; 3) for patients with generation or second-generation TKI patients with all stages of treatment failure can be considered for allo-HSCT according to the patient’s age and willingness; 4) allo-HSCT is preferred for patients with T315I mutation at any time during TKI therapy; 5) patients in accelerated or acute phase.      It is recommended to give TKI treatment at least until complete hematologic remission before transplantation and to stop TKI for at least 2 weeks before transplantation. Those who cannot receive TKI also need to be treated with hydroxyurea/trichostatin/other chemotherapy and receive allo-HSCT after complete hematologic remission. Jiang Qian et al. from Peking University People’s Hospital published an article in Blood for patients in accelerated phase of CML taking imatinib or performing The results showed that a history of chronic granulomatous disease >12 months, hemoglobin <100 g/L, and peripheral blood primitive cells ≥5% were three independent poor prognostic factors, and patients were classified as high, intermediate, or low risk according to these three factors, i.e., patients with two or more of the three factors were considered high risk, those with any one factor were considered intermediate risk, and those with no poor prognostic Patients with any one of these factors were considered to be at low risk. Low-risk patients treated with imatinib alone and allo-HSCT achieved similarly good event-free survival (EFS), progression-free survival (PFS), and overall survival (OS), all greater than 80%. There was no difference in EFS and OS in intermediate-risk patients, but there was a difference in PFS, 55.7% in the imatinib group and 92.9% in the allo-HSCT group, p=0.047. For high-risk patients, 5-year EFS, PFS and OS were 9.3%, 18.8% and 17.7%, respectively, in the imatinib group, and 5-year EFS, PFS and OS in the allo-HSCT group were 66.7%, 100% and 100%, respectively, with statistically significant differences.      (2) Donor and transplantation protocol selection HLA-identical siblings are still the best donor of choice for transplantation in CML patients. However, with the improvement of HLA matching accuracy, the incidence of graft-versus-host disease (GVHD) in unrelated donor transplants has decreased significantly, and the long-term survival rate of patients after transplantation has converged with that of sibling donor transplants, a conclusion supported by domestic studies. Therefore, if a CML patient has an indication for transplantation, an HLA-compatible unrelated donor may be considered even when a sibling donor is not available. For patients in chronic phase with T315I mutation, patients with poor response, failure or intolerance to second-generation TKI therapy or patients in accelerated or acute phase, HLA-hybrid donor HSCT can be selected based on the transplantation unit's experience in HLA-hybrid transplantation and the patient's wishes when no HLA-hybrid donor is available.      In the choice of transplantation protocol, the clear marrow pretreatment protocol is the most widely used standard transplantation protocol, especially for patients in the accelerated and acute phases. Domestic studies have also shown that the use of imatinib in patients in the accelerated and acute phases back to the chronic phase before transplantation significantly reduces the risk of relapse and has mild drug toxicity. For patients in the chronic phase, there is no definitive conclusion as to whether clearing or reduced dose pretreatment regimens are better or worse. However, because of the relatively low transplantation-related complications, reduced-dose pretreatment regimens are increasingly used in older age groups and in those who want to preserve some fertility.      (3) Post-allo-HSCT monitoring Post-allo-HSCT monitoring includes: hematological examination, bone marrow cytogenetic karyotyping or FISH, and molecular genetic analysis (RQ-PCR BCR-ABLmRNA) is recommended if available ① Achieving complete cytogenetic remission: Those who achieve complete cytogenetic remission after transplantation should undergo bone marrow/peripheral blood quantitative polymerase chain reaction (RQ-PCR) monitoring every 3 months for 2 years, followed by every 6 months for 3 years. If the test result is positive, BCR-ABL kinase should be tested for mutations, and ①TKI therapy should be selected according to the test result; ②discontinuation of immunosuppression; ③donor lymphocyte infusion (DLI); ④interferon (IFNa) therapy; ⑤new drug trials are feasible in units that are qualified to conduct new drug clinical trials; ②non-remission or relapse: those who are not in remission or relapse after transplantation should stop immunosuppression (ii) non-remission or relapse: those who are not in remission or relapse after transplantation should stop immunosuppressive treatment and be tested for mutations in BCR-ABL kinase at the same time, and select TKI therapy; donor lymphocyte infusion (DLI); interferon (IFNa) therapy; chemotherapy; second transplantation, TKI therapy or chemotherapy is recommended before transplantation, at least until complete hematological remission; new drug trials are feasible in units that are qualified to conduct new drug clinical trials.       (iii) Prevention: There are reports of good efficacy in CML patients with continued treatment with TKI for 1 year from 3 months after transplantation as a measure to prevent relapse. Therefore, prophylactic TKI therapy can be considered for patients who are eligible for it.