Mixed Phenotype Acute Leukemia: Patient Outcomes According to the WHO 2008 Classification

Mixed phenotype acute leukemia (MPAL) is a rare leukemia with features of both myeloid and lymphoid lineage. The 2008 World Health Organization (WHO) definition of MPAL is based on the expression of strictly specific T-lymphoid (cytoplasmic CD3) and myeloid (myeloperoxidase) antigens, and B-cell lineage assignment relies on the expression of CD19 together with other B cell–associated markers (Borowitz et al. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. 2008). In this retrospective review, we analyzed the clinical features and treatment outcomes of patients treated at MDACC between 5/2004 and 6/2012 who fulfilled the diagnostic criteria for MPAL. We identified a total of 41 patients with a median age of 47 years (range 9 – 82; 63% male) with characteristics described in the table below. Twenty one (51%) patients had leukemia with myeloid plus B-lymphoid (M/B) markers, 18 (44%) with myeloid plus T-lymphoid (M/T) markers, and 2 (5%) with B-lymphoid plus T-lymphoid (B/T) markers. Cytogenetic analysis showed 31 patients (76%) had an abnormal karyotype, with most commonly a complex karyotype (37%). Sixteen patients received hematopoietic stem cell transplantation (HSCT) in first remission (n=9) or with active disease (n=7) following a myeloablative (n=10) or reduced intensity (n=6) conditioning regimen. The median survival from the time of diagnosis was 19 months (range, 1 – 82 months). On univariate analysis, complete response to induction therapy was a significant predictor of survival (65% vs. 9%, p<.001).  Additionally, there was a trend toward better overall survival for patients who received HSCT compared with the patients who were treated with chemotherapy alone (60% versus 35%, p=.083). Differences in immunophenotypic subtypes or karyotype did not impact the overall survival.

Patients with MPAL represent a rare and heterogeneous category of leukemia with poor prognosis. The stricter classification schema should help to lessen heterogeneity and allow for better understanding of the leukemia, and ultimately better patient outcomes. Our small series suggests that response to induction portends better survival.  Furthermore, hematopoietic stem cell transplantation can further improve outcomes.

 

	Transplant (n=16)	Chemotherapy (n=25)
Age, median (range)	42 (19-66)	52 (9-82)
Sex
Male	9	17
Female	7	8
Immunophenotypic Subtypes
B/My	11	10
T/My	4	14
B/T	1	1
Cytogenetic
Diploid	3	7
Complex	6	9
Ph+	1	3
MLL	2	0
Others	4	6
Induction
Lymphoid	7	13
Myeloid	3	2
Hybrid	6	10
Response
Complete Remission	12	15
No Response	4	10
Status at Transplant
First Complete Remission	9	-
Primary Induction Failure	4	-
Active disease	3	-
Transplant Regimen
Myeloablative	10	-
Reduced Intensity	6	-
Donor
Matched Related	6	-
Matched Unrelated	8	-
Mismatched	2	-