Clinical Characteristics and Outcomes of Infant Acute Lymphoblastic Leukemia from a Single Institute in China
Authors: Li Xiaolan , Liu Fang , Wan Yang , Guo Ye , Chen Xiaojuan , Chen Yumei , Zou Yao , Zhang Li , Zhu Xiaofan , Yang Wenyu 
Published: December 2024

Objective: To examine the clinical features and prognosis of infant acute lymphoblastic leukemia (IALL) patients from a single center. Methods: A retrospective analysis of clinical data and prognosis was conducted on 25 IALL cases from the Pediatric Blood Diseases Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from November 2004 to June 2024. Patients were categorized into KMT2A-Rearrangement (KMT2A-R) positive, KMT2A-R negative, and KMT2A-R unknown groups based on FISH results. Their prognoses were compared using Kaplan-Meier and Log-Rank tests to analyze relapse-free survival. Results: Of the 25 IALL cases, 8 were male and 17 female, with an average onset age of 268 (40, 355) days. Immune classification by flow cytometry was achieved in 21 cases, all showing B-ALL with CD19 expression. Among these, 9 had a pro-B phenotype, 8 pre-B phenotype, 1 common B phenotype, and 3 were unspecified. CD10 expression was tested in 18 cases, with 8 positive and 10 negative. Out of 17 cases with chromosome karyotype results, 12 were abnormal. there were 4 with t(4;11), 1 with t(11;19), 1 with t(1;11), 3 with other abnormalities, and 3 with complex karyotypes. FISH for KMT2A-R was performed on 18 cases, with 13 testing positive. Real-time PCR further identified 6 cases as KMT2A::AF4, 3 as not KMT2A::AF4, 3 as KMT2A::ENL, and 1 as MLL::AFF2. Out of 18 cases evaluated for the central nervous system (CNS), 13 were classified as CNS1, 3 as CNS2, and 1 as CNS3. A total of 17 patients consented to induction therapy, while the rest discontinued treatment after diagnosis. Among these, 13 patients received 4-week VDLD induction (vincristine, daunorubicin, L-asparaginase/pegaspargase, dexamethasone), 1 patient was treated with 2-week venetoclax and 5-day azacytidine, 1 patient received 2-week VP (vincristine, dexamethasone) and 2-week blinatumomab, and 2 patients underwent 4-week VDLV induction (vincristine, dexamethasone, pegaspargase, venetoclax). Efficacy evaluations were conducted for 15 patients, of whom 14 achieved complete remission (CR) with negative minimal residual disease (MRD), and 1 patient achieved CR with an MRD level of 0.01%. 13 patients followed the CCCG-ALL protocols similar to pediatric patients, while 4 followed the CCCG-iALL/MPAL-2022 protocols for consolidation and maintenance. The 17 patients had a median follow-up of 16.9 months, ranging from 1.5 to 78.2 months. The 3-year relapse-free survival (RFS) rate was 50.0±16.7%. There was no significant difference in 3-year RFS between the KMT2A-R positive group (11 cases) and the KMT2A-R negative group (4 cases) (37.5±20.3% vs. 66.7±27.2%, P=0.668). It is noteworthy that the patient treated with VP and blinatumomab, despite presenting with a high white blood cell count exceeding 100×10^9/L at diagnosis and the KMT2A::AF4, achieved complete remission with a brief period of agranulocytosis during VP treatment, experiencing only mild infection during blinatumomab and incurring low costs for anti-infection drugs. The patient adhered to the CCCG-iALL/MPAL-2022 protocols for a duration exceeding two years and remains in the first remission. Conclusions: IALL patients frequently have KMT2A-R and exhibit high relapse rates and poor prognosis. Considering the toxicity associated with intensive induction chemotherapy, combining reduced-intensity chemotherapy with blinatumomab may provide a more cost-effective therapeutic strategy.