Outcomes of Mixed Phenotype Leukemia, Not Otherwise Specified (NOS), in Adults: A Single Centre Retrospective Review from 2000 to 2014
Authors: Bhella Sita D. , Musani Rumina , Porwit Anna , Tierens Anne , Gupta Vikas , Schimmer Aaron D. , Schuh Andre C , Yee Karen W.L. , Minden Mark D. 
Published: October 2019

Introduction:

Acute leukemias of ambiguous lineage (AUL), biphenotypic leukemias (BAL) and mixed phenotypic leukemias (MPAL) are a heterogeneous group of rare, poorly characterized leukemias with unfavorable outcomes. AUL, BAL and MPALs are believed to constitute 2-5% of all leukemias. The optimal treatment regime for this group of leukemias is currently unknown.

The primary objective of this study is to determine the complete remission rate (CR) and overall survival (OS) among adult patients with mixed phenotypic leukemia, not otherwise specified (NOS), as defined by the WHO 2008 classification criteria.

Methods:

Patients with mixed phenotype acute leukemia (MPAL) older than 17 years of age who were treated at Princess Margaret Cancer Centre from January 1, 2000 to June 30, 2014 were identified through the Leukemia Database at Princess Margaret Cancer Registry. Pathology review of the original diagnostic bone marrow was completed to ensure patients met the WHO 2008 criteria for MPAL, not otherwise specified (NOS). Patients with MLL+, BCR-ABL+, PDGRFA+ were excluded from analysis.

Results:

Fourteen patients were identified and confirmed by pathology review. Eleven (79%) were male, 3 (29%) were female. The median age was 57 years (range: 18-84). Eight (57%) had extramedullary involvement at presentation. Six (42%) had poor risk cytogenetics, whereas 8 (57%) had intermediate risk cytogenetics at presentation as per the MRC criteria. Two patients (14%) had p53 mutations/loss of chromosome 17. Four patients (42%) had monosomy 7 karyotype. Six cases (43%) were myeloid/B, seven cases (50%) were myeloid/T and one (7%) was myeloid/T/B type. The median WBC at presentation was 10.8 x 109/L (2.3 x 109/L-106 x 109/L).

Five patients were treated upfront with daunorubicin and cytarabine (3&7) with 1 of these patients achieved a CR with this upfront regime. Five patients were treated upfront with the Dana Farber Consortium Protocol (DFCI) and 4 of these patients achieved a CR with this upfront regime. Two patients were treated upfront with HyperCVAD, and 1 achieved a CR. Two patients were treated palliatively. One received azacytidine as palliative treatment and achieved a CR with a duration of 5 months. Ten (71%) of these patients achieved a CR. Three of the primary nonresponders achieved a CR with an alternative induction regime. The median CR1 duration was 5.5 mos (range, 2-40 mos).

Overall median survival was 13 mos (95% CI, 8 mos-27 mos). The OS at 1 year and 2 years was 56% (95% CI, 29%- 82%) and 32% (95% CI, 6%-57%), respectively.

Four patients (29%) underwent an allogeneic hematopoietic stem cell transplant. At last follow up, 13 of the 14 patients have died, 11 from relapsed leukemia and 2 from sepsis post HCT. One patient died of relapsed leukemia post HCT.

Conclusions:

This retrospective review confirms the high risk nature and poor prognosis of MPAL NOS. Our limited cohort showed a male predominance, a high rate of extramedullary involvement at presentation, and a higher rate of CR with DFCI as the initial remission induction regime. HCT or other forms of maintenance therapy should be considered in CR1 in eligible patients due to the high- risk nature of MPAL NOS.

Disclosures

Gupta: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding.