Acute Promyelocytic Leukemia Workup

  • Author: Sandy D Kotiah, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Aug 2, 2011
 

Laboratory Studies

The initial laboratory workup of acute promyelocytic leukemia (APL) should include a complete blood cell (CBC) count with differential, peripheral blood smear, comprehensive metabolic profile for baseline renal and liver function tests, electrolyte levels, prothrombin time (PT) and activated partial thromboplastin time (aPTT), fibrinogen measurements.

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Other Tests

Many authorities recommend lumbar puncture at diagnosis of acute promyelocytic leukemia (APL) in high-risk patients (see Treatment, Medical Care) who present with a very high white blood cell (WBC) count. In these cases, the CNS may serve as a sanctuary site warranting intrathecal therapy. Coagulopathy should be corrected first, and lumbar puncture may sometimes be delayed until after induction therapy.

The cerebrospinal fluid (CSF), in addition to routine chemical and hematologic studies, should be cytospun and examined by a pathologist trained in examination of fluid cytospins. Flow cytometry of CSF should be done to look for the abnormal clonal cells.

Also, cardiac function should be examined by echocardiography or scintigraphy before the administration of anthracyclines.

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Procedures

A bone marrow biopsy with aspirate should be performed immediately. The sample should be sent for flow cytometry and cytogenetics. In addition, fluorescent in situ hybridization (FISH) for the translocation or reverse transcription–polymerase chain reaction (RT-PCR) for the PML-RAR alpha transcript should also be done. The typical phenotype of acute promyelocytic leukemia (APL) is myeloperoxidase positive and CD33 positive, human leukocyte antigen (HLA)-DR negative.

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Histologic Findings

There are different morphologic variants of acute promyelocytic leukemia (APL), which include the following[7] :

  • The hypergranular subtype (classic M3) has frequent Auer rods, clumps of granular material containing lysosomes, peroxidase, lysosomal enzymes, and large crystalline inclusions (see Image 4 or below). Auer rods can be seen in other types of AML, but they are usually seen in acute promyelocytic leukemia (APL). The nucleus is folded or bilobed, and the cytoplasm contains prominent azurophilic granules. The bone marrow is usually hypercellular. The cells stain intensely for Sudan black and myeloperoxidase, but not for periodic acid-Schiff (PAS) and HLA-DR. Regularly hypergranular subtype of acute promyelocRegularly hypergranular subtype of acute promyelocytic leukemia. Image courtesy of Dr. William Kocher.
  • The microgranular variant (M3v) also has a folded nucleus, but the cytoplasm has fine, dusky granules and Auer rods are rare. It is seen in 25% of cases of acute promyelocytic leukemia (APL).
  • The hyperbasophilic subtype shows an increased nucleocytoplasmic ratio and strongly basophilic cytoplasm with blebs. There are few granules and no Auer rods.
  • The last variant is PLZF-RAR alpha (M3r), and it has regular, condensed chromatin in the nucleus. There are fewer granules and rare Auer rods when compared with the hypergranular subtype.
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Staging

The appropriate workup of acute promyelocytic leukemia (APL) should include a bone marrow biopsy and aspiration, with aspirate samples sent for flow cytometry, cytogenetics, and FISH for the usual translocations. The role of lumbar puncture and CSF examination is debated, but many authorities recommend CSF examination in patients who present with significant leukocytosis. The FAB classification system has been replaced by the WHO classification system. The FAB classification categorized leukemia based on cell morphology, including cytochemical stains, whereas the WHO system also includes flow cytometry, cytogenetic studies and, in some cases, clinical information.

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Contributor Information and Disclosures
Author

Sandy D Kotiah, MD  Fellow in Hematology Oncology, Thomas Jefferson University Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Specialty Editor Board

Clarence Sarkodee-Adoo, MD  Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program

Disclosure: Takeda Millenium Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Ronald A Sacher, MB, BCh, MD, FRCPC  Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgments

I would like to acknowledge Dr. Emmanuel Besa for allowing me the opportunity to write this article.

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Bone marrow aspirate hybridized with the RARA dual color break-apart probe set (Abbott-Vysis). The cell to the left shows a normal cell with 2 fusion signals, as the 5'RARA probe (orange) and the 3'RARA probe (green) are not separated. The cell on the right shows split signals for one RARA gene, indicating a chromosomal rearrangement disrupting the RARA gene. Image courtesy of Dr. Tina Edmonston from the Department of Pathology at Thomas Jefferson University Hospital.
Bone marrow aspirate hybridized with PML/RARA dual color translocation probe set (Abbott-Vysis). The cell to the right shows a normal cell with 2 separate PML (orange) and RARA (green) signals each. The cell to the left shows an abnormal cell characterized by a single fusion signal juxtaposing the PML and RARA signals, suggestive of a translocation of the 2 genes. Images courtesy of Dr. Tina Edmonston from the Department of Pathology at Thomas Jefferson University Hospital.
Hypogranular subtype of acute promyelocytic leukemia. Image courtesy of Dr. William Kocher.
Regularly hypergranular subtype of acute promyelocytic leukemia. Image courtesy of Dr. William Kocher.
 
 
 
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