What is the optimal induction regimen for patients with biphenotypic acute leukemia? Should they be treated with AML-type or ALL-type induction regimens?
I like HAM (high-dose cytarabine and mitoxantrone) for younger fit patients.
Most studies , including our experience, recommend ALL-based protocol for better outcome (Ex; CVAD protocol). However, these recommendations need to be taken with caution because of the patients’ heterogeneity and/or the small numbers included.
Most data available at present advocate an intensive ALL type regimen (Such as Hyper CVAD or St Jude Total XIII-B) with early transplant. Needless to say, a suitable TKI should be added if a Philadelphia chromosome is associated.
Article Mixed-phenotype acute leukemia: Historical overview and a ne...
It seems that in biphenotype cases for two point we must be aware , 7+3 regimen is standard for both leukemia but because ALL line of this case is high risk for CNS involvement .
The choice must be consist of this point , high dose cytozar is best choice
ALL-type
Pui C-H, Sandlund JT, Pei D, Campana D, Rivera GK, Ribeiro RC,
et al. Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St. Jude Children’s Research Hospital. Blood 2004;104:2690-6.
Both ALL and AML have the same CR rates, but the work of Matures suggest a benefit of maintenance as in ALL regimens. Nevertheless is an aggressive disease still with short survival and allogeneic HSCT is also recommended.
All the answers above suggest the best choices. I would also suggest perfect immunophenotyping and check for translocations. Is the leukemia biphenotypic or biclonal, i.e. has AML and ALL populations? Or does it have only aberrant expression of one ALL or AML marker? Phenotype shall be obtained before chemo and patient be screened for the presence of m.r.d. based on the phenotypes of clones. Of note, I saw also AUL (acute undifferentiated leukemia) once - in AUL, AML like induction probably works better.
All type. And TKI if a Philadelphia chromosome is associated.
We use ALL treatment and stratify according to MRD after induction. We do not recommend hSCT unless the MRD is unsatisfactory, which follows the same guidelines as other ALL subtypes.
We use high-risk ALL protocol for these patients and we decide the postconsolidation therapy (chemotherapy or alloHSCT) according to the MRD levels after induction and consolidation
High risk ALL protocol is preferable and then re -evaluate the patient after induction regarding complete remission.
It depends also of the flow cytometric features, if the majority of blasts from MPAL cases show expression of myeloid- and lymphoid-restricted markers, and of course t(9;22)/BCR-ABL1.
I would like to emphasize about the detailedimmunophenotypic data to decision.
But its true that ALL-directed treatment seems more effective with a higher
response rate and better outcome compared with an AML or to an
AML ALL schedule, according this paper:
Blood 117 p. 3163-71
http://www.ncbi.nlm.nih.gov/pubmed/21228332
Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification
Estella Matutes, Winfried F Pickl, Mars Van't Veer, Ricardo Morilla, John Swansbury, Herbert Strobl, Andishe Attarbaschi, Georg Hopfinger, Sue Ashley, Marie Christine Bene, Anna Porwit, Alberto Orfao, Petr Lemez, Richard Schabath, Wolf-Dieter Ludwig (2011)
MPAL is a rare group of acute leukemias. No specific treatment exists for this disease. It seems that ALL-like chemotherapy regimen should be given, nevertheless prognosis is still poor. Allogeneic stem cell transplantiion or investigational protocols should be offered. Minimal residual disease-based protocols could be helpful as in ALL patients.
WHO classification included those Ph+ cases and TKI could be of help. I have not read publications regarding efficacy of TKI in MPAL patients, but there is a rationale for its use.
We use AML type induction if the blasts express myeloperoxidase in the flow cytometry and ALL type otherwise.
The protocol for ALL seems better than that of AML in Japan, that includes variety of drugs including anthracyclin, High dose Arac and High Dose MTX. But some patients with biphenotipic leukemia have good prognosis only after the chemotherapy, therefore, SCT should be scheduled according to the genetic analysis including chromosomal analysis or each clinical course.
If patent nas AML with coexpression of limphoid antigens 7+3 with. Cladribine (DAĆ) can be optimal induction.
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