Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia

Munker, Reinhold; Brazauskas, Ruta; Wang, Hai Lin; Lima, Marcos de; Khoury, H. Jean; Gale, Robert Peter; Maziarz, Richard T.; Sandmaier, Brenda M.; Weisdorf, Daniel J.; Saber, Wael

doi:10.1016/j.bbmt.2016.02.013

Cited by 40 publications

(38 citation statements)

References 17 publications

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“…Extramedullary involvement (particularly CNS) is reported to be more frequent in comparison to ALL or AML. This difference can be partly explained by a relatively higher occurrence of hyperleukocytosis at the diagnosis 27 . The molecular biology background and its prognostic importance in MPAL is not well known, but may contribute to risk-stratification and treatment management.…”

Section: Discussionmentioning

confidence: 91%

“…31 ). Median age at diagnosis varies in series between 20 and 35 years with bimodal age distribution 14,21,27 . The reason is probably due to biology and differentiation potential into mixed-lineage leukemic cells in leukemogenesis of childhood ALL or AML more common in the elderly population.…”

Section: Discussionmentioning

confidence: 99%

“…The reason is probably due to biology and differentiation potential into mixed-lineage leukemic cells in leukemogenesis of childhood ALL or AML more common in the elderly population. In most MPAL case series male patients predominated similarly to AML or ALL in large population-based studies 3,6,14,21,27,32 . Future research of genetic and hormonal characteristics, environment exposures are likely to provide insight into the observed sex differences.…”

Section: Discussionmentioning

confidence: 99%

“…No difference in survival was observed between patients who underwent HCT in first or second CR (ref. 27 ). When selecting adequate therapy, all available information should be included such as patientage, comorbidities, clinical condition and their primary disease (morphology, cytogenetics, immunophenotyping).…”

Section: Treatment Of Mpalmentioning

confidence: 99%

“…It is assumed that MPAL arising from a hematopoietic stem cell (with strong CD34+ expression and a potential to differentiate into various lineages) will not be curable by chemotherapy alone 19,20,25 . As in Ph1+ ALL, AML arising from MDS or with adverse cytogenetics, incurable without allogeneic HCT, the role of transplantation in the first complete remission is similar in mixed-phenotype leukemia [25][26][27][28] . The use of a protocol for ALL with a broader spectrum of cytostatic drugs in the first cycle of chemotherapy seems to be more reasonable than of protocols for AML therapy 15,25 .…”

Section: Treatment Of Mpalmentioning

confidence: 99%

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Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification and treatment

Čerňan¹,

Szotkowski²,

Pikalova³

2017

BIOMED PAP

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Mixed-phenotype acute leukemia (MPAL) is a heterogeneous group of hematopoietic malignancies in which blasts show markers of multiple developmental lineages and cannot be clearly classified as acute myeloid or lymphoblastic leukemias. Historically, various names and classifications were used for this rare entity accounting for 2-5% of all acute leukemias depending on the diagnostic criterias used. The currently valid classification of myeloid neoplasms and acute leukemia published by the World Health Organization (WHO) in 2016 refers to this group of diseases as MPAL. Because adverse cytogenetic abnormalities are frequently present, MPAL is generally considered a disease with a poor prognosis. Knowledge of its treatment is limited to retrospective analyses of small patient cohorts. So far, no treatment recommendations verified by prospective studies have been published. The reported data suggest that induction therapy for acute lymphoblastic leukemia followed by allogeneic hematopoietic cell transplantation is more effective than induction therapy for acute myeloid leukemia or consolidation chemotherapy. The establishment of cooperative groups and international registries based on the recent WHO criterias are required to ensure further progress in understanding and treatment of MPAL. This review summarizes current knowledge on the diagnosis, classification, prognosis and treatment of MPAL patients.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Treatment Of Mpalmentioning

confidence: 99%

Section: Treatment Of Mpalmentioning

confidence: 99%

See 3 more Smart Citations

Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification and treatment

Čerňan¹,

Szotkowski²,

Pikalova³

2017

BIOMED PAP

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Rare Acute Leukemias

Smith

Webster

2017

Textbook of Uncommon Cancer

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Prognostic impact of Philadelphia chromosome in mixed phenotype acute leukemia (MPAL): A cancer registry analysis on real‐world outcome

2020

Self Cite

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Mixed phenotype acute leukemia (MPAL) is thought to have poor outcome, and presence of the Philadelphia chromosome (Ph+) has been considered to be an adverse prognostic marker. However, most of these reports were in the pre‐tyrosine kinase inhibitors (TKIs) era. Recent limited reports indicate improved outcomes for MPAL with the addition of TKIs. We examined the outcomes of 241 cases of MPAL according to the 2008 WHO classification from the Surveillance, Epidemiology, and End Results registry. The MLL+ patients had a median age of 6 years while other subtypes occurred mostly in adults and had comparable age. On multivariate analyses and after adjustment for age, year of diagnosis and chemotherapy status, Ph+ MPAL patients had reduced risk of death in comparison to Ph(–) MPAL patients (hazard ratio [HR] = 0.28, P = .002). So, MLL+ MPAL had the worst outcome with a 10‐fold increased risk of death in comparison to Ph+ MPAL patients (HR = 10.2, P < .001). Importantly, the outcome of Ph+ MPAL was comparable to Ph+ acute lymphoblastic leukemia in a 1:1 matched case‐control analysis. In conclusion, this is the largest registry study which examines the outcomes of MPAL subtypes. We confirm that MPAL is a heterogenous disease. Note, Ph+ MPAL nowadays has a better OS in comparison to other subtypes and is comparable to Ph+ ALL patients. This is most likely secondary to changes in practice and more utilization of TKIs. On the other hand, MLL rearrangement is associated with infantile MPAL and has a dismal prognosis.

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Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia

Cited by 40 publications

References 17 publications

Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification and treatment

Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification and treatment

Rare Acute Leukemias

Prognostic impact of Philadelphia chromosome in mixed phenotype acute leukemia (MPAL): A cancer registry analysis on real‐world outcome

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