Combination chemotherapy plus dasatinib leads to comparable overall survival and relapse‐free survival rates as allogeneic hematopoietic stem cell transplantation in Philadelphia positive acute lymphoblastic leukemia

Abstract

Background The Philadelphia chromosome is associated with a poor prognosis in acute lymphoblastic leukemia (ALL). While hematopoietic stem cell transplantation (HSCT) has been regarded as a favorable treatment option in adult Philadelphia‐positive (Ph+) ALL, its benefit is less clear in the era of newer generation tyrosine kinase inhibitors (TKIs) like dasatinib. Methods This was a retrospective study that analyzed the outcomes of adult patients with Ph+ ALL treated with either combination chemotherapy plus dasatinib or combination chemotherapy plus dasatinib followed by allogeneic HSCT. Results A total of 70 patients were included; 30 (42.9%) underwent allogeneic HSCT while 40 (57.1%) received only chemotherapy plus dasatinib. In comparing overall survival (OS) rates, results between the 2 groups were similar with a 1‐year OS of 93.3% versus 100% (P = 0.20), 2‐year OS of 89.8% versus 86.2% (P = 0.72), and 3‐year OS of 76% versus 71.3% (P = 0.56) in the transplant versus nontransplant groups, respectively. The 3‐year relapse‐free survival (RFS) rates were also similar at 70.5% in the transplant group and 80.1% in the nontransplant group (P = 0.94). Subgroup analyses were performed for patients with specific poor prognostic factors (higher white blood count, older age, positive minimal residual disease status), but results again showed no significant survival difference between transplant and nontransplant patients. Conclusions While HSCT has historically led to a survival advantage in Ph+ ALL, the results of our study demonstrate that it may have a less beneficial role in the era of newer generation TKIs such as dasatinib.

Is stem cell transplantation still needed for adult Philadelphia chromosome-positive acute lymphoblastic leukemia receiving tyrosine kinase inhibitors therapy?: A systematic review and meta-analysis

“…I 2 = 73%) [11,16,26,30,33,36,37] (S4A and S4B Fig) . In addition, the pooled result between allo-HSCT group and auto-HSCT group were not significantly different (pooled OR of OS 0.93; 95% CI, 0.54-1.60; I 2 = 0%) [14,25] (S4C Fig).…”

“…Subgroup analysis of studies with all Ph + ALL patients achieving CR1 prior to allo-HSCT or CMT showed increased pooled OR of OS to 1.75 (95% CI, 1.00-3.06; I 2 = 64%) [10,11,16,24,26,30,33,34,36,37] while pooled OR of DFS was decreased to 2.69 (95% CI, 1.27-5.72;…”

“…OS rate was defined as the ratio of patients who were still alive since the diagnosis date at a particular time of interest [14][15][16]. DFS and CIR rates were defined as the proportion of patients who did not have a relapse or death and the ratio of patients who had a relapse, after complete remission at the time of interest, respectively [12,14].…”

“…For TKI treatment, imatinib was the most commonly used in 22 studies, with a dose range of 400-800 mg/day [9-13, 15, 17, 22, 23, 25, 27-38]. Dasatinib is used in nine studies, with a dose range of 70-140 mg/day [10,12,16,24,29,[35][36][37][38], ponatinib PLOS ONE is used in two studies, with a dose range of 15-45 mg/day [26,36], and nilotinib is used in two studies, with a dose range of 600-800 mg/day [35,38]. Regarding post-transplant TKI, it is given to all patients in nine studies [9,12,16,25,27,30,33,37], to some patients in six studies [13-15, 26, 36, 38], to none of the patients in one study [31], and no report of post-transplant TKI in ten studies [10,11,17,23,24,28,29,32,34,35].…”

“…For the outcomes of allo-HSCT and CMT groups, a total of 19 and 13 studies reported OS rates (as 2-year rate by one study [27], 2.5-year rate by one study [29], 3-year rate by six studies [10,16,26,30,33,34], 4-year rate by four studies [9,12,15,37] and 5-year rate by seven studies [11,17,24,28,31,32,36]) and DFS rates (as 2-year rate by one study [26], 3-year rate by three [15] and 5-year rate by one study [31]) and CIR rates (8-month rate by one study [29], 2-year rate by one study [27], 3-year rate by one study [30], 4-year rate by three studies [12,15,37] and 5-year rate by three studies [11,31,36]), respectively. The pooled meta-analysis showed that Ph + ALL patients who received allo-HSCT had a significantly prolonged OS and DFS compared to those who received only CMT with pooled odds ratio (OR) of 1.61 (95% CI, 1.08-2.40; I 2 = 59%) and 3.23 (95% CI, 2.00-5.23; I 2 = 62%), respectively (Fig 2A and 2B).…”