B-cell acute lymphoblastic leukemia (B-ALL) is a hematological malignancy in which the bone marrow produces neoplastic lymphoblasts that are committed to the B-cell lineage. The complexity and spectrum of hematological malignancies highlight the importance of clinicopathologic correlation with the availability of ancillary studies . Approximately 20–30% of adult ALLs harbor the Philadelphia chromosome, which produces the
This was a retrospective, single-center, observational study in the Department of Hematology at the Hospital Ampang, Selangor Malaysia, which is a national hematology referral center in Malaysia. A total of 176 patients with B-ALL underwent allogeneic SCT at the Hospital Ampang, Malaysia between 2006 and 2018. All patients diagnosed with
MRD evaluations at 3 different TPs were analyzed: post-induction (TP1), post-consolidation or week 16 (TP2), and end of treatment (TP3).
CMR was defined as the absence of detectable
Continuous variables are summarized using the median and range. Categorical variables are summarized using the count (N) and proportion (%). Differences between subgroups were assessed with t-test, ANOVA, or Kruskal-Wallis test, depending on the sample size and distribution. Associations between categorical variables were analyzed using the chi-square test or Fisher’s exact test. Probabilities of OS and DFS were calculated using the Kaplan-Meier method, and differences between subgroups were tested using the log-rank test. The prognostic significance of baseline and transplantation covariates was determined using the Cox proportional hazard regression model. Covariates were selected based on statistical significance in the univariate analysis, which included MRD status and treatment responses. A prognostic factor was considered statistically significant if the
The study included a total of 96 patients (42 males and 54 females) with a median age of 37.5 years (range, 14–69 yr). Eight patients (8.3%) were in the adolescent age group of 12 to 19 years old, and 45 patients (46.9%) were young adults aged 20–39 years. The remaining 43 patients (44.8%) were aged 40 years and above. The most common ethnic group was Malay (50%, N=48), followed by Chinese (38.5%, N=37) and Indian (14%, N=19). Over half of the patients (53.1%) presented with a high white blood cell count (>30×109/L), with a median of 36×109/L. A total of 49 patients received the GMALL/BFM protocol (51%), whereas 47 patients (49%) received the HyperCVAD protocol. Of the 96 patients, 62 received TKIs, mostly imatinib, during chemotherapy and were still receiving TKIs as maintenance therapy at the time of SCT. All patients who underwent SCT received TKIs and chemotherapy (19 received imatinib, 13 received nilotinib, and 1 received dasatinib). Of the 38 patients who underwent SCT, 33 received allogeneic stem cells and 5 received autologous stem cells (Table 1).
A total of 33 patients (34.4%) who completed chemotherapy were transplant-eligible and underwent allogeneic SCT. The median age of transplant recipients was 37 years (range, 15–59 yr). All patients received allografts, with the majority being from a matched-sibling donor (N=27) (Table 2). Most patients (87.9%, N=29) underwent myeloablative conditioning chemotherapy, with a total body irradiation-based protocol being the main conditioning regimen (66.7%). Thirteen patients (44.8%) developed acute graft-versus-host disease (GVHD) and 14 (50.0%) developed chronic GVHD. MRD status based on the pre-transplant
At the time of analysis, 20 patients were alive (60.6%), whereas 13 died (39.4%), as shown in Table 2. With a median follow-up of 25 months, the median OS was not reached. With a median follow-up of 9 months, the median DFS was not reached. Six (46.2%) of 13 patients with MMR experienced relapse, with a median time to relapse of 14 months (range, 8–104). The 2-year, 3-year, and 5-year OS rates were 66.3%, 58.7%, and 53.4%, respectively, and the 2-year, 3-year, and 5-year DFS rates were 63.7%, 59.9%, and 54.5%, respectively (Fig. 1D).
It is widely accepted that MRD monitoring is paramount when considering the best treatment options for patients with
With our low non-relapse mortality rate in matched-sibling donor transplants, it was justifiable to perform SCT in ALL patients with standard risk in CR1, given the significantly higher rate of relapse and lower DFS among patients who did not undergo SCT. This echoed earlier observations of the UKALL/RCOG 2993 studies, which showed significant differences in survival between the transplanted and non-transplanted cohorts, even in ALL patients with standard risk , and they did not perform MRD monitoring or identification of high-risk genetic markers. Reports showing successful transplants in CR2 with a curative potential of 25–30% have been reported [24, 25]. However, these reports were highly selective and did not influence decisions against earlier transplants. In our retrospective observation, other factors, such as age, sex, and
We showed that pre-transplant
Patients who achieved CMR at 3 months had better OS and DFS than those who did not, regardless of whether they received chemotherapy or allogeneic SCT. Although there was a trend for better survival among patients treated with chemotherapy, the difference was not statistically significant. However, the relapse rate was higher in the chemotherapy group. The higher non-relapse mortality in patients who underwent allogeneic SCT may have contributed to this discrepancy. Therefore, chemotherapy plus TKIs may be an option for patients who achieve early CMR but are unwilling to undergo SCT.
Relapse or disease progression post-SCT remains a problem , as these patients have an extremely poor prognosis. Novel immunotherapies such as inotuzumab and blinatumomab, as well as chimeric antigen receptor T-cell therapy, have provided an opportunity for patients with relapsed or refractory ALL [25, 27]. Blinatumomab has been shown to eliminate MRD in ALL patients and has led to better survival outcomes post-SCT . In this study, 6 patients with
Our study focused on allogeneic SCT in the largest cohort of adult
In conclusion, end-of-treatment MMR was associated with a lower relapse rate and higher DFS among patients with
This study was approved by the Medical Research and Ethics Committee of the Ministry of Health Malaysia (NMRR-19-2833-47785), with the approval of the Malaysia Director-General of Health. Special thanks to all clinical and laboratory staff of the Haematology Department, Ampang Hospital, for data collection.
No potential conflicts of interest relevant to this article were reported.