Aberrant Expression of Myeloid Antigens Identifies a Subgroup of Standard-Risk Adult Acute Lymphoblastic Leukemia Patients with Short Survival

Background:

Adult patients (pts) with acute lymphoblastic leukemia (ALL) are stratified into standard- and high-risk groups based on WBC count, karyotype and response to induction chemotherapy. Nevertheless, the standard-risk group (SR) is heterogeneous with 40%-50% of pts relapse, and the survival varies from a few months to decades. The role of immunophenotyping in further sub-stratifying the standard risk group has not been assessed in adult pts.

Patients and Methods:

Out of 161 adult ALL pts diagnosed and treated at the L/BMT Program of BC between 1989 and 2010, 81 SR pts were separated out based on: WBC ≤50X10⁹/L ( B-ALL) or ≤100X10⁹/L (T-ALL), absence of adverse cytogenetics  (i.e. t(9;22), BCR-ABL fusion, complex karyotype (≥5 abnormalities), t(4;11), t(1;19), low hypodiploid/near triploid), and complete remission (CR) following induction chemotherapy. The immunophenotype of this group was reviewed, reanalyzed, and correlated with CR, relapse, relapse-free survival (RFS), and overall survival (OS). Pts were treated with a consistent chemotherapy regimen: Induction consisted of prednisone, vincristine and daunorubicin ± L-asparaginase. A second phase of induction comprised of cyclophosphamide, cytarabine, methotrexate and mercaptopurine.  Intensification was with dexamethasone, vincristine, daunorubicin, cyclophosphamide, cytarabine and thioguanine. Four cycles of consolidation with cytarabine and tenoposide were given followed by 2-year maintenance oral chemotherapy with methotrexate and mercaptopurine.

Results:

Eighty-one standard-risk adult ALL pts (62 B-ALL, 19 T-ALL) were identified, (50 males , 31 females), median age 33 years (16-66). With a median follow up of 30 months (3-235), 32 pts (40%) relapsed within 1-136 months. The median OS and RFS were 30 months (3-235) and 26 months (1-235) respectively. CD13, CD33 and CD117 data was available in 59, 58 and 50 pts respectively. They were positive in 17 (29%), 13 (22%) and 0 (0%) pts respectively. At least one of CD13 or 33 or 117 was available in 61, and positive in 25 of them (41%). Aberrant expression of myeloid antigens was associated with early relapse (median 8 vs 16 months), shorter survival (median 11 vs 28 months). OS at 24 months and 60 months and RFS at 24 months were inferior in ALL patients expressing myeloid antigens (table-1).

Table-1 Association of Expression of Myeloid Antigens with Survival in Adult ALL
Short Survival	CD13	CD33	CD13 or 33 or 117
RFS  ≤24 months	44% vs 16%, p=0.014	35% vs 13%, p=0.044	57% vs 27%, p=0.018
OS ≤24 months	50% vs 16%, p=0.006	35% vs 16%, p=0.095	64% vs 28%, p=0.006
OS ≤60 months	34% vs 8%, p=0.979	24% vs 17%, P=0.591	46% vs 23%, p=0.138

 

Conclusion:

In adult patients with standard-risk ALL, aberrant expression of myeloid antigens indicates early relapse, and inferior RFS and OS at 24 and 60 months. More aggressive therapy may be considered in this subgroup.