Pediatric Acute Biphenotypic Leukemia (aBL): A Clinico-Pathologic Analysis of a Single Institution Experience.
Authors: Crosswell Hal E. , Yost Robert B. , Phillips Carol N. , Holden Jeannine , Briones Michael , Daniel Bergsagel J. , Woods William G. , Lew Glen 
Published: October 2019

Current classification of childhood leukemia relies on morphologic, immunophenotypic, and molecular characteristics. aBL is rare and poorly understood. We retrospectively evaluated 7 patients diagnosed with aBL according to European Group for Immunological Classification of Leukemias (EGIL) criteria(2 or more lineages with a score greater than 2).

Among 269 leukemia patients diagnosed in 2001–2004, 7 (2.6%) were classified as having aBL. Clinical characteristics/course and laboratory data are listed below in Tables1&2.

TABLE 1: CLINICAL CHARACTERISTICS & COURSE PATIENT AGE SEX RACE INITIAL WBC TREATMENT COURSE 1 12 F AA 5,600 CCG1961-> CCG2891, HDARAC, HSCT IND. FAILURE; R1:CNS,BM R2:BM R3:CNS,BM DOD, 24M 2 17 F C 81,600 CCG2891 R1:CNS,BM DOD, 10M 3 2 M C 40,000 CCG1961 RER; CR1, 16M 4 2 M H 5,630 CCG1991-> CCG1961, HSCT SER; CR1, 14M 5 6 F H 38,000 CCG1961 RER; CR1, 12M 6 16 M AA 150,000 CCG1961-> AAML03P1 IND. FAILURE; R1:BM DOD, 9M 7 11 M C 77,100 AAML03P1, HSCT RER; CR1, 7M Table 2: MORPHOLOGY, IMMUNOPHENOTYPE & CYTOGENETICS PATIENT FAB MORPHOLOGY FLOW CYTOMETRY EGIL SCORE(T/B/M) CYTOGENETICS/FISH * =Peripheral Blood 1* L1, M5 CD3, CD7, pCD5, CD33,MPO 3.5/0/3 6,XX,add(1)(p22);t(3;12)(p24;p13),del(6)(q21q22),del(8)(p21),-9,del(13)(q13q14), +22 2* L1, M2 P1: CD19, CD22, CD33, Tdt P2: CD2,CD14,CD15, CD33, MPO 2/3.5/4 46,XX,der(8)t(8;?;17)(q11.2;?;q21),der(9)t(8;9)(q21.2;p12),del(15)q21), der(17)t(15;?;17)(q21;?;q11.2) 3 L2 P1: CD33, CD34 P2: CD13, CD15, CD10, CD19, CD22 0/4/2.5 46, XY, del12p-/TEL deletion 4 L1 CD19,CD22, CD13, CD15, CD33 0/3/2.5 46, XY 5 L1, M5 CD19, pCD20, CD22, CD13, CD15, pCD33 3.5/0/3.5 46, XY, del(5)(q15q33), dic(7;9)(p11.2;p12),inv(9)c,t(10,11)(p13;q21) 6 L2 cCD3, pCD5, CD7, CD13, CD15, CD33,pCD117 0/4/3.5 46, XX/Trisomy 10 7* L1, M5 CD2,CD3,CD7, TdT, pCD22,CD13, CD15, pMPO, CD117 4/1/4.5 46, XY

5 patients had abnormal karyotypes and/or FISH studies; none had MLL rearrangements or t(9;22). Induction treatment consisted of AML-type therapy (CCG 2891 /COG AAML03P1) in 2 patients who achieved CR by day 28. Two patients received ALL-type therapy (CCG 1961) and entered CR by Day 28. Three patients required dose intensification due to induction failure: 2 switched from ALL to AML-type therapy. Post induction chemotherapy was given in 4 cases; allogeneic HSCT in 3 cases (2 in CR1; 1 in 2nd relapse). 2/4 and 2/3, respectively, remain alive in 1st CR after chemotherapy or HSCT. All 3 deaths were from relapse of aBL within 2 yrs from diagnosis & occured in adolescents with complex karyotypes. In our experience, pediatric aBL represents a high risk population, especially in adolescents. Intensive induction chemotherapy is necessary in the majority of cases to achieve CR, although it is unclear whether ALL or AML-type therapy is superior. MLL & t(9;22) may not be as common in pediatric aBL as previously described. Collaborative trials and biologic studies are clearly needed for better understanding and outcomes.