Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid

Park, Jae H.; Qiao, Baozhen; Panageas, Katherine S.; Schymura, Maria J.; Jurcic, Joseph G.; Rosenblat, Todd L.; Altman, Jessica K.; Douer, Dan; Rowe, Jacob M.; Tallman, Martin S.

doi:10.1182/blood-2011-04-346437

Cited by 345 publications

(281 citation statements)

References 35 publications

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“…Conventional treatment (anthracycline 1 ATRA) for APL is usually reported to cure >80% of patients, although, because of early death, this may occur in only 60-70% of patients in community settings [28]. To dispense with chemotherapy MD Anderson investigators administered, in a single-arm trial, only ATO1ATRA to patients presenting with WBC < 10,000 [29].…”

Section: Treatmentmentioning

confidence: 99%

Acute myeloid leukemia: 2013 update on risk‐stratification and management

2013

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Disease overviewAcute myeloid leukemia (AML) results from accumulation of abnormal blasts in the marrow. These cells interfere with normal hematopoiesis, can escape into the peripheral blood, and infiltrate CSF and lung. It is likely that many different mutations, epigenetic aberrations, or abnormalities in micro RNA expression can produce the same morphologic disease with these differences responsible for the very variable response to therapy, which is AMLs principal feature.DiagnosisThis rests on demonstration that the marrow or blood has > 20% blasts of myeloid lineage. Blast lineage is assessed by multiparameter flow cytometry, with CD33 and CD13 being surface markers typically expressed by myeloid blasts. It should be realized that clinical/prognostic considerations, not the blast % per se, should be the main factor determining how a patient is treated.Risk StratificationTwo features determine risk: the probability of treatment‐related mortality (TRM) and, more important, even in patients aged >75 with Zubrod performance status 1, the probability of resistance to standard therapy despite not incurring TRM. The chief predictor of resistance is cytogenetics, with a monosomal karyotype (MK) denoting the disease is essentially incurable with standard therapy even if followed by a standard allogeneic transplant (HCT). The most common cytogentic finding is a normal karyotype(NK) and those of such patients with an NPM1 mutation but no FLT3 internal tandem duplication (ITD), or with a CEBPA mutation, have a prognosis similar to that of patients with the most favorable cytogenetics (inv 16 or t[8;21]) (60–70% cure rate). In contrast, NK patients with a FLT3 ITD have only a 30–40% chance of cure even after HCT. Accordingly analyses of NPM1, FLT3, and CEBPA should be part of routine evaluation, much as is cytogenetics. Risk is best assessed considering several variables simultaneously rather than, for example, only age. Increasing evidence indicates that other mutations and abnormalities in microRNA (miRNA) expression also affect resistance as do post treatment factors, in particular the presence of minimal residual disease. These newer mutations and MRD are discussed in this update.Risk‐adapted therapyPatients with inv (16) or t(8;21) or who are NPM1+/FLT3ITD—can receive standard therapy (daunorubicin + cytarabine) and should not receive HCT in first CR. It seems likely that use of a daily daunorubicin dose of 90 mg/m2 will further improve outcome in these patients. There appears no reason to use doses of cytarabine > 1 g/m2 (for example bid X 6 days), as opposed to the more commonly used 3 g/m2. Patients with an unfavorable karyotype (particularly MK) are unlikely to benefit from standard therapy (even with dose escalation) and are thus prime candidates for clinical trials of new drugs or new approaches to HCT; the latter should be done in first CR. Patients with intermediate prognoses (for example NK and NPM and FLT3ITD negative) should also receive HCT in first CR and can plausibly receive either investigational or standard induction therapy, with the same prognostic information about standard therapy leading one patient to choose the standard and another an investigational option. This update discusses results with newer agents: quizartinib and crenolanib, gemtuzumab ozogamicin, clofarabine and cladribine, azacitidine and decitabine, volasertib, and means to prevent relapse after allogeneic transplant.The diagnosis of AML essentially is made as it was in 2012. Thus this review will emphasize new developments in risk stratification and treatment using as references many papers published in 2012. Am. J. Hematol. 88:318–327, 2013. © 2013 Wiley Periodicals, Inc.

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Section: Treatmentmentioning

confidence: 99%

Acute myeloid leukemia: 2013 update on risk‐stratification and management

2013

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“…ED, the term proposed 20 years ago when ATRA had not been widely used, 94 has recently attracted attention again from investigators. 33,95,96 Park et al 97 reported 1400 cases of APL from 1992 to 2007, the overall ED rate was 17.3%, and only a modest change in ED was observed over time. Lehmann et al 98 reported 105 cases of APL patients among whom the frequency of ED (within 30 days) actually reached 29%, a rate significantly higher than those in non-APL AML, especially evident in the elderly (460 years) population.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…Our aim is to deliver the most timely and best treatment to each newly diagnosed APL patient, that is, to mobilize our entire human and material resources if necessary, including emergency room, intensive care unit, multi-disciplinary team of physicians and nurses, to ensure the maximum saving of lives at the onset of disease. More importantly, as Park et al 97 mentioned, there is a clear need to provide the knowledge necessary to recognize APL as a medical emergency that requires specific and simultaneous actions, including a prompt initiation of ATRA, aggressive supportive care to counteract the coagulopathy and transfer to experienced medical centers when the disease is first suspected.…”

Section: Future Perspectivesmentioning

confidence: 99%

How to manage acute promyelocytic leukemia

et al. 2012

Leukemia

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“…A second problem are early deaths in APL. The early death rate in population-based studies [12] is always higher than early death rate in patients enrolled on clinical trials. Investigators from France looked at all patients from a specific geographic area who developed APL to try to determine if rapid institution of ATRA, which ameliorates the associated coagulopathy, would be effective in reducing the early mortality rate.…”

Section: Richard M Stonementioning

confidence: 99%

Highlights in acute myeloid leukemia from the 2012 meeting of the American Society of Hematology

Stone

2013

Expert Review of Hematology

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Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid

Cited by 345 publications

References 35 publications

Acute myeloid leukemia: 2013 update on risk‐stratification and management

Acute myeloid leukemia: 2013 update on risk‐stratification and management

How to manage acute promyelocytic leukemia

Highlights in acute myeloid leukemia from the 2012 meeting of the American Society of Hematology

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