PF191 RECLASSIFICATION OF BIPHENOTYPIC ACUTE LEUKEMIA INTO MIXED‐PHENOTYPE ACUTE LEUKEMIA ACCORDING TO WHO CRITERIA REFINES PATIENT CHARACTERIZATION AND PROGNOSIS; DISEASE MARKERS AND IMPACT ON OUTCOME
Authors: Douka V. , Kotta K. , Chatziioannidis A. , Iskas M. , Athanasiadou A. , Papathanasiou M. , Lalayanni C. , Syrigou A. , Tachynopoulou V. , Avramidou R. , Vadikolia C. , Tsompanakou A. , Anagnostopoulos A. 
Published: June 2019

Background:

MPAL is a heterogeneous category in the World Health Organization (WHO) that comprises acute leukemias with discrete admixed populations of myeloid and lymphoid blasts (“bilineal”) or with extensive coexpression of lymphoid and myeloid markers in a single blast population (“biphenotypic”). Mixed phenotype acute leukemia (MPAL) accounts for 2–5% of newly diagnosed acute leukemia. WHO criteria highlight key lineage‐defining markers with particular emphasis on CD19 for B lineage, CD3 for T lineage, and myeloperoxidase (MPO) for myeloid lineage.

Aims:

Review of classification, biology, clinical features, and treatment approach to MPAL.

Methods:

We studied retrospectively 1163 consecutive patients diagnosed with acute leukemia at the G. Papanicolaou Hospital, Thessaloniki, Greece, from 1999 until January 2019 subclassified as follows: AML = 854, B‐ALL = 172, T‐ALL = 80, acute undifferentiated leukemia = 9, MPAL/BAL = 44, diagnosed using either the WHO (13/44) or the EGIL (31/44) criteria.

Results:

Of the 31 patients diagnosed with biphenotypic acute leukemia (BAL) using the EGIL classification 12 did not fulfill the WHO criteria for MPAL. Only 2 B‐Myeloid cases according to the WHO classification did not fulfill EGIL criteria. We reclassified all cases following the WHO criteria and resulted in 32 MPAL cases (2.8% of the cohort; 24/32 B‐Myeloid, 7/32 T‐Myeloid, 1/32 B‐T‐MPAL).

Aberrant T‐cell marker expression was seen in 6 patients with B‐Myeloid MPAL, CD7 expression being the most frequent. In T‐Myeloid MPAL, the cytoplasmic CD79a B‐cell marker was aberrantly expressed in 4/7 cases (57%). HLA‐DR was expressed in all MPAL cases. TdT was positive in all Ph+ MPAL, compared to 26% in non‐Ph+ MPAL cases. Seventy‐three percent of the cases were classified as ALL by morphology. Clinical data was available in 25/32 patients; 18 males, 7 females, median age: 32 years (2–79). Median WBC count at presentation was 10.6  × 109/L, hemoglobin 9.3 g/dL, platelets 63  × 109/L, LDH 839 IU/L and marrow blast count 55%. Cytogenetic data available for 29/32 patients were as follows; normal karyotype = 5 (17.2%), t(9;22) translocation = 7 (24.1%), complex karyotype (CK) = 14(48.2%), monosomy 7 = 5 cases (17.2%).

Response to treatment and outcome were available for 24 and 29 patients, respectively; 18 received ALL‐type therapy, 3 received AML‐type therapy, 2 a combination of ALL+AML therapy. All Ph+ patients received Tyrosine Kinase Inhibitor (TKI). One died before receiving treatment. ALL‐type treatment induced a response in 13/18 patients (72%), whereas AML‐type in 33.3%; both patients who received combination therapy responded. All refractory patients (7/24) had a complex karyotype. Fourteen patients underwent allogeneic hematopoietic cell transplantation (allo‐HCT). Median overall survival (OS) was 18.7 months; 12 and 27 months for patients with CK and t(9;22) respectively, while the 5‐year survival rate was 12.5%. In contrast, BAL patients classified according to EGIL had median OS 23.3 months.

Summary/Conclusion:

In our study, reclassification of BAL (EGIL) patients as per WHO, resulted in a more accurate characterization of acute leukemias with mixed phenotypic features. Our study confirms that MPAL/BAL displays a uniformly poor outcome especially in patients with CK. The addition of TKI in the treatment of Ph+ patients probably ameliorates MPAL poor prognosis. Upon validation in larger prospective cohorts, MPAL could be considered as an independent poor risk feature for leukemia patients.