Clinical and lab findings
A total of 198 newly diagnosed B-ALL patients, including 21 BAL patients, were admitted to CHCMU and CWCCH between January 2017 and November 2019, and 3 BAL patients with MLL transcripts were identified, accounting for 1.37% of the B-ALL population. The clinical and laboratory findings for the 3 reported patients are listed in Table 1. BM samples were obtained at diagnosis, and the results of the BM examinations are listed in Table 2, Fig. 1 and Fig. 2.
Treatment And Prognosis
Pt 1 and Pt 2 were treated with the B-NHL-2009 protocol, and Pt 3 was treated with the CCCG-ALL-2015 protocol. They achieved complete remission (CR) according to morphological, FCM and molecular examination after one course of chemotherapy. Allogenic haematopoietic stem cell transplantation (allo-HSCT) was considered by clinicians and was refused by the parents of the patients. A total of six courses of chemotherapy were completed for Pt 1 and Pt 2; as of the last follow-up in January 2020, these two patients had a CR status, and their event-free survival (EFS) times were 32 and 29 months, respectively. Chemotherapy was continued for Pt 3, and the EFS time was 3 months.
The literature was searched in the abovementioned databases, and 12 articles involving 24 patients suffering from BAL with MLLr were found. Clinical and laboratory findings, BM examination results, and the treatment and prognosis of these cases in the literature reports are listed in Tables 3, 4 and 5 [8, 9, 17–26].
Data from 27 patients suffering from BAL with MLLr, including the 3 patients described in our articles, were collected and analysed. Thirteen males and 14 females were included, and the average and median age at diagnosis was 19.5 ± 4.95 m and 12 m, respectively (ranging from 6 wk to 9 year); 14 (51.85%) and 24 (88.89%) patients were ≤ 1 and ≤ 2 years of age, respectively. Renal, testicular, CNS and skin involvement at diagnosis were present in 6, 1, 4 and 3 patients, respectively. The average white blood cell (WBC) and platelet (PLT) counts and haemoglobin (Hb) levels were 87 ± 35.24 × 109/L, 69.96 ± 5.38 × 109/L and 65.12 ± 12.34 g/L, respectively.
Twenty-six (96.30%) of the 27 patients showed non-ALL-L3 morphology, and 1 patient presented with ALL-L3 morphology. The mature B-ALL phenotype was confirmed by FCM in all 27 patients. Expression of CD19, CD22, and sIgM with light-chain restriction was detected, and TdT and CD34 were not present in most cases. Expression of CD20 was found in 25 patients. Interestingly, negative or suspicious expression of CD20 was found in 16 (64%) patients, and positive expression of CD20 was detected with a monoclonal antibody in 9 (36%) patients. Although 2 of 3 patients in our report presented with positive CD20 expression, the expression level of CD20 was less than 30%.
Chromosomal karyotype results were reported for 26 patients, while 2 patients had no metaphase chromosomes to be analyzed; 11q23-related abnormal karyotypes were found in 11 patients. Results of FISH of MLLr were reported in 23 patients, and 22 (95.65%) cases were positive. The results of the detection of MLLr transcripts were presented for 16 patients. Fourteen patients were positive and were found to have MLL-AF9 (6 cases), MLL-AF1 (2 cases), MLL-AF10 (2 cases), and MLL-ENL (2 cases), while 1 patient did not have a clear result. FISH may be the most accurate tool for the detection of MLLr. t(8;14) and its variant were not detected by karyotyping; MYCr was detected by FISH in 17 patients, and the results were negative.
The 27 patients who received chemotherapy included patients treated with ALL-like (12 cases), BL (8 cases) or Interfant-99  (7 cases) protocols. One patient died of sepsis, 1 patient presented with refractory status, and 25 patients achieved CR, and the CR rate was 92.59%. In addition, 6 patients received allo-HSCT, 1 (16.67%) patient relapsed 6 months later, and the prospective 2-yr EFS (pEFS) was 83.33%, as reported in the literature. Nineteen patients subsequently received chemotherapy according to the Interfant-99 (6 cases), BL (6 cases) or ALL-like (7 cases) protocols, and 9 (47.37%) of them relapsed. The 2-yr pEFS was 41.91% (Fig. 3). Four patients in the Interfant-99 and BL groups relapsed, and the 2-yr pEFS in these groups were 40% and 33.33%, respectively. One patient in the ALL-like group relapsed, but the median value of follow-up was only 5 m.