Highlights•WBC counts ≥ 30 × 109/L at diagnosis, MMR failure after second consolidation chemotherapy, and nontransplantation are independent poor prognostic factors for Ph+ ALL patients.•Transplant is a viable option for all Ph+ ALL patients and is superior to the combination of TKIs and chemotherapy, conferring significant survival advantages, especially in high- and intermediate-risk patients.•Outcomes of TKIs combined with chemotherapy and transplant are equally good in low-risk patients.AbstractHere we compare outcomes between the tyrosine kinase inhibitors (TKIs) plus chemotherapy regimen and allogeneic hematopoietic stem cell transplantation (transplantation cohort) in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) and explore factors associated with prognosis. Data from 145 Ph+ ALL patients were analyzed retrospectively. Patients were treated with imatinib plus chemotherapy and then transplantation or continuous TKIs with chemotherapy based on patient preference. A total of 145 Ph+ ALL patients were recruited for this study (median age, 37 years; range, 14 to 65). Among these patients, 81 were men (55.9%) and 86 underwent IKZF1 detection, which identified 59 patients (68.6%) with IKZF1 deletions. After treatment 136 patients (95.8%) achieved complete remission (CR) eventually. With a median follow-up of 33 months (range, 4 to 114) for CR patients, 77 patients (57.9%) underwent transplantation and 56 (42.1%) received continuous TKIs with chemotherapy. At the 4-year follow-up the cumulative incidence of relapse (CIR), disease-free survival (DFS), and overall survival (OS) were 29.4% (95% confidence interval [CI], 24.9% to 34.4%), 60.9% (95% CI, 56.5% to 65.3%), and 69.2% (95% CI, 65.1% to 73.3%), respectively. Multivariate analysis showed that WBC counts < 30 × 109/L at diagnosis (hazard ratio [HR], 4.2; 95% CI, 1.9 to 9.2; P < .001; HR, 2.6; 95% CI, 1.4 to 4.9; P = .003; HR, 2.7; 95% CI, 1.4 to 5.4; P = .003), 3-log reduction of BCR-ABL levels from baseline after 2 consolidation cycles (HR, 4.4; 95% CI, 1.9 to 9.9; P < .001; HR, 3.1; 95% CI, 1.7 to 5.9; P < .001; HR, 3.5; 95% CI, 1.9 to 8.7; P = .001; defined as "minimal residual disease low level"), and transplantation (HR, 5.0; 95% CI, 2.2 to 11.2; P < .001; HR, 3.3; 95% CI, 1.7 to 6.4; P < .001; HR, 4.1; 95% CI, 1.9 to 8.7; P < .001) were the favorable factors of CIR, DFS, and OS. According to the first 2 risk factors, CR patients were divided into 3 groups: low risk (no factor, n = 42, 31.6%), intermediate risk (1 factor, n = 73, 54.9%), and high risk (2 factors, n = 18, 13.5%). In the low-risk group at the 4-year follow up no significant difference existed between the transplant and nontransplant arms for the probabilities of CIR (8.5% versus 7.7%, P = .671), DFS (88.2% versus 83.9%, P = .426), and OS (96.6% versus 83.3%, P = .128). In the intermediate- and high-risk groups at the 4-year follow-up, CIR (23.6% versus 36.9%, P = .017; 37.5% versus 100.0%, P < .001), DFS (62.4% versus 43.8%, P = .048; 56.2% versus 0%, P < .001), and OS (76.1% versus 47.7%, P = .037; 51.4% versus 6.3%, P = .001) rates were significantly better in the transplant arm than in the nontransplant arm. In surviving patients of the low-risk group, no difference in complete molecular response (CMR) rates (85.7% versus 72.7%, P = .379) between the transplant and nontransplant arms was found. However, in the intermediate-risk group the proportion of CMR was significantly higher in the transplant arm than in the nontransplant arm (82.8% versus 42.9%, P = .006). In the high-risk group 4 of 7 transplant patients (57.1%) were in CMR, and no patients survived in the nontransplant arm. Allogeneic hematopoietic stem cell transplantation confers significant survival advantages for Ph+ ALL patients compared with TKIs plus chemotherapy, especially in intermediate- and high-risk patients.
Summary There is an urgent need for an oral, efficient and safe regimen for high‐risk APL under the pandemic of COVID‐19. We retrospectively analysed 60 high‐risk APL patients. For induction therapy (IT), in addition to all‐trans retinoic acid (ATRA) and oral arsenic (RIF), 22 patients received oral etoposide (VP16) as cytotoxic chemotherapy (CC), and 38 patients received intravenous CC as historical control group. The median dose of oral VP16 was 1000 mg [interquartile rage (IQR), 650–1250]. One patient died during IT in the control group, 59 evaluable patients (100%) achieved complete haematological remission (CHR) after IT and complete molecular remission (CMR) after consolidation therapy. The median time to CHR and CMR was 36 days (33.8–44) versus 35 days (32–42; p = 0.75) and 3 months (0.8–3.5) versus 3.3 months (2.4–3.7; p = 0.58) in the oral VP16 group and in the control group. Two (9.1%) and 3 (7.9%) patients experienced molecular relapse in different group respectively. The 2‐year estimated overall survival and event‐free survival were 100% versus 94.7% ( p = 0.37) and 90.9% versus 89.5% ( p = 0.97) respectively. A completely oral, efficient and safe induction regimen including oral VP16 as cytoreductive chemotherapy combined with ATRA and RIF is more convenient to administer for patients with high‐risk APL.
<div>AbstractPurpose:<p>Although myeloablative HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT) following pretransplant anti-thymocyte globulin (ATG) and granulocyte colony-stimulating factor (G-CSF) stimulated grafts (ATG+G-CSF) has been confirmed as an alternative to HSCT from HLA-matched sibling donors (MSD), the effect of haplo-HSCT on postremission treatment of patients with acute myeloid leukemia (AML) with intermediate risk (int-risk AML) who achieved first complete remission (CR1) has not been defined.</p>Patients and Methods:<p>In this prospective trial, among 443 consecutive patients ages 16–60 years with newly diagnosed <i>de no</i>vo AML with int-risk cytogenetics, 147 patients with molecular int-risk AML who achieved CR1 within two courses of induction and remained in CR1 at 4 months postremission either received chemotherapy (<i>n</i> = 69) or underwent haplo-HSCT (<i>n</i> = 78).</p>Results:<p>The 3-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher in the haplo-HSCT group than in the chemotherapy group (74.3% vs. 47.3%; <i>P</i> = 0.0004 and 80.8% vs. 53.5%; <i>P</i> = 0.0001, respectively). In the multivariate analysis with propensity score adjustment, postremission treatment (haplo-HSCT vs. chemotherapy) was an independent risk factor affecting the LFS [HR 0.360; 95% confidence interval (CI), 0.163–0.793; <i>P</i> = 0.011], OS (HR 0.361; 95% CI, 0.156–0.832; <i>P</i> = 0.017), and cumulative incidence of relapse (HR 0.161; 95% CI, 0.057–0.459; <i>P</i> = 0.001) either in entire cohort or stratified by minimal residual disease after the second consolidation.</p>Conclusions:<p>Myeloablative haplo-HSCT with ATG+G-CSF is superior to chemotherapy as a postremission treatment in patients with int-risk AML during CR1. Haplo-HSCT might be a first-line postremission therapy for int-risk AML in the absence of HLA-MSDs. Haplo-HSCT might be superior to chemotherapy as a first-line postremission treatment of intermediate-risk AML in CR1.</p></div>
To evaluate the efficacy of interferon-α (IFN-α) as maintenance therapy in patients with favorable-risk acute myeloid leukemia (AML), this retrospective study enrolled 84 patients with favorable-risk AML: 42 patients who received IFN-α maintenance therapy and 42 patients who did not (control). The median follow-up time and duration of IFN-α treatment was 26 (6–54) months and 18 (2–24) months, respectively. The 4-year estimated relapse-free survival (RFS) after the last consolidation chemotherapy was 86.8% (95% confidence interval (CI), 75.8–97.8%) in the IFN-α group and 55.7% (95% CI, 37.2–74.3%) in the control group (p=.007). The 4-year estimated overall survival was 94.4% (95% CI, 86.8–102%) and 76.4% (95% CI, 61.9–90.9%) in IFN-α and control groups, respectively (p=.040). The Cox regression analysis showed that IFN-α treatment was the only independent factor affecting RFS (p=.004). Maintenance therapy with IFN-α may prevent relapse in favorable-risk AML after consolidation chemotherapy.
Summary No consensus has been reached on the relationship between CBFB‐MYH11 copies and prognosis. Of 1525 acute myeloid leukemia (AML) patients, 58 with CBFB‐MYH11‐positive AML (16/58 patients with c‐kit mutation) were retrospectively analyzed with a median follow‐up duration of 29.8 (range: 4.8–74.4) months. Of these, 25/58 (43.1%) patients underwent allogeneic hematopoietic stem cell transplantation (allo‐HSCT), 10 of whom had the c‐kit mutation. Of the 33 patients who did not undergo allo‐HSCT, recurrence in patients with CBFB‐MYH11/ABL level >0.1% at any time after two consolidation cycles was significantly higher than in patients with CBFB‐MYH11/ABL level <0.1% (61.9% vs. 0%, P = 0.001); further, the 3‐year relapse‐free survival (RFS; 31.4% vs. 100%, P = 0.004) and event‐free survival (EFS; 33.1% vs. 100%, P = 0.004) were significantly decreased in patients with CBFB‐MYH11/ABL level >0.1% at any time after two consolidation cycles. The 3‐year RFS and EFS rates were lower in patients who did not receive allo‐HSCT than in those who did (31.4% vs 84.6%, P = 0.000; 31.4% vs. 80.8%, P = 0.001). CBFB‐MYH11‐positive AML patients with CBFB‐MYH11/ABL level >0.1% at any time after two cycles of consolidation had poor prognoses, and allo‐HSCT could improve their survival.
To compare the efficacy and toxicity of 10 mg/m² or 8 mg/m² idarubicin (Ida) combined with cytarabine (IA"3+7"regimen) as induction chemotherapy for adult patients with newly diagnosed acute myeloid leukemia (AML).From June 2004 to October 2013, 335 adult AML (non acute promyelocytic leukemia) patients receiving the IA regimen as induction chemotherapy were enrolled, including 198 cases with 10 mg/m² Ida and 137 cases with 8 mg/m² Ida for 3 days. We compared the hematologic response, hematologic side effects and prognosis between the two regimens.Except for 4 early deaths, the complete remission (CR) rate after the first cycle of induction chemotherapy was 72.5%, 10.0% partial remission (PR) and 82.5% overall remission (OR) rate. The CR and OR rates were higher in the 10 mg/m² Ida group than the 8 mg/m² Ida group (CR: 78.9% vs 63.5%, P=0.003; OR: 88.2% vs 75.4%, P=0.007). Multivariate analysis showed that female, HGB≥100 g/L, FLT3-ITD mutation negative and 10 mg/m² Ida were favorable factors for CR. All patients presented cytopenias of grade Ⅳ. There was no differences on the recovery time of ANC≥0.5×10⁹/L and PLT≥20×10⁹/L after induction chemotherapy. Within a median follow-up of 14 (1-118) months, 98 (29.3%) patients relapsed, 92 (27.5%) died. The disease-free survival (DFS) and overall survival (OS) at 3 years were 53.2% and 58.9%, respectively. DFS and OS at 3-year were 34.2% and 37.4% in the chemotherapy cohort, 74.5% and 81.2% in the transplant cohort. 10 mg/m² Ida was an independent favorite factor for DFS (P=0.040) and OS (P=0.007).As compared to 8 mg/m², 10 mg/m² Ida significantly improved the CR, with the same extent of hematological side effects, and was an independent favorite factor for DFS and OS.
To evaluate the molecular response and prognostic factors of patients with Philadelphia chromosome/BCR-ABL-positive acute lymphoblastic leukaemia (Ph⁺ ALL) treated by imatinib with chemotherapy.From May 2006 to July 2012, 82 adult Ph⁺ ALL patients were enrolled in the study. Forty-eight patients combined imatinib in, and 34 patients after induction therapy. Forty-nine patients underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) after 3 to 5 cycles of consolidation therapy. The molecular response of BCR-ABL mRNA was evaluated by real-time quantitative PCR in every chemotherapy course ending.The complete remission (CR) rate after the first cycle of induction chemotherapy was 76.8% (63/82), with overall CR rate of 92.7% (76/82). The CR rate in the patients combined imatinib in was higher than of those combined imatinib after the first cycle of induction chemotherapy (93.8% vs 52.9%, P<0.001). 55.3% patients BCR-ABL decreased >1 log after induction therapy. Among 76 CR patients, cumulative incidence of relapse was 27.6%, the probabilities of disease-free survival (DFS) and overall survival (OS) at 3 years were 60.5% and 70.2%, respectively. allo-HSCT was an independent favorable factor for decrease of leukemia relapse (P<0.001). allo-HSCT, imatinib combined in the first cycle of induction therapy and female were independent favorable factors for DFS (P<0.01, 0.05 and 0.01, respectively), BCR-ABL mRNA reduction at least 1 log from baseline after the first induction therapy and allo-HSCT were independent favorable factors for OS (P=0.011 and 0.027, respectively).Imatinib combined in the first cycle of induction therapy, BCR-ABL mRNA reduction at least 1 log from baseline after the first induction therapy and allo-HSCT improved outcomes of Ph⁺ ALL patients.
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