1Department of Laboratory Medicine, Ajou University School of Medicine, Suwon, Korea.
2Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea.
3Department of Pediatrics, Ajou University School of Medicine, Suwon, Korea.
4Department of Laboratory Medicine, Kosin University Gospel Hospital, Busan, Korea.
5Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea.
6Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul, Korea.
7Department of Laboratory Medicine, Dankook University College of Medicine, Cheonan, Korea.
8Department of Laboratory Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
Acute promyelocytic leukemia (APL) can be life threatening, necessitating emergency therapy with prompt diagnosis by morphologic findings, immunophenotyping, cytogenetic analysis, or molecular studies. This study aimed to assess the current routine practices in APL and the clinico-pathologic features of APL.
We reviewed the medical records of 48 Korean patients (25 men, 23 women; median age, 51 (20-80) years) diagnosed with APL in 5 university hospitals between March 2007 and February 2012.
The WBC count at diagnosis and platelet count varied from 0.4 to 81.0 (median 2.0)×109/L and 2.7 to 124.0 (median 54.5)×109/L, respectively. The median values for prothrombin time and activated partial thromboplastin time were 14.7 (11.3-44.1) s and 29 (24-62) s, respectively. All but 2 patients (96%) showed a fibrin/fibrinogen degradation product value of >20 µg/mL. The D-dimer median value was 5,000 (686-55,630) ng/mL. The t(15;17)(q22;q12 and
Since APL is a medical emergency and an accurate diagnosis is a prerequisite for prompt treatment, laboratory support to implement faster diagnostic tools to confirm the presence of
Acute promyelocytic leukemia (APL) is a well known type of acute myeloid leukemia (AML) with characteristic biological and clinical features, which include the presence of the chromosomal translocation t(15;17)(q22;q12) resulting in the fusion of the promyelocytic leukemia (
The current standard for induction therapy is the simultaneous combination of ATRA with anthracycline-based chemotherapy, which results in an extremely high antileukemic efficacy, achieving a 90% to 95% complete remission rate [6, 7]. Because the detection of
This study was undertaken to assess the current routine practice in APL, with a focus on whether the genetic test results are available by the time that therapeutic decisions are made. The clinico-pathologic features of APL were also assessed.
Forty-eight Korean patients, who were newly diagnosed with APL between March 2007 and February 2012 in 5 university hospitals, were included in this study. We reviewed the clinical and laboratory findings of the patients, such as age, gender, complete blood cell (CBC) counts, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrin/fibrinogen degradation product (FDP), D-dimer, bone marrow (BM) study, immunophenotyping, chromosome analysis, molecular study, and therapeutic regimens administered. We also investigated the turnaround time (TAT) of laboratory tests confirming the presence of t(15;17) (chromosome analysis) or
This study was performed under the approval of Ajou University Hospital Institutional Review Board. The flow cytometric analysis for immunophenotyping, chromosome analysis, and molecular studies were carried out according to the same methods as our previous study .
The demographic characteristics and laboratory features of the 48 APL patients are summarized in Table 1. All the patients were adults except for one. Prolonged PT was observed in 38 (81%) out of 47 patients tested, and prolonged aPTT in 6 patients (13%). Increased FDP and D-dimer were observed in all of the 39 patients tested.
The results of fluorescent
APL is uncommon in children under 10 years of age and is mostly prevalent in midlife. Most of the demographic and laboratory characteristics of our patients (Table 1), including immunophenotype and distribution of
All 48 patients revealed the markers t(15;17) or
In previous studies, secondary cytogenetic abnormalities have been reported in 26% to 40% of cases, and among them, trisomy 8 was reported as the most frequent abnormality, with ider(17)(q10) accounting for only 1% to 3% [20, 21]. However, in the present study, ider(17) was observed in 5 patients (10.4%), being the second most frequently observed additional chromosomal abnormality following trisomy 8. Although the significance of this finding remains to be fully elucidated, it is noteworthy that ider(17) is one of the most common additional chromosomal aberrations in the Korean population.
Ever since the introduction of ATRA in front-line therapy APL has been considered to be the most curable subtype of AML [22, 23]. Despite the great improvement in APL treatment, early death due to severe bleeding is one of the major problems in APL, which occurs in approximately 5-10% of newly diagnosed cases . The life-threatening bleeding problems associated with disseminated coagulopathy require instant treatment with ATRA, and the correct diagnosis should be considered as a medical emergency in a patient with APL, requiring a fast and accurate diagnosis, preferably within hours .
However, the genetic (molecular) techniques are time consuming: 1-2 d for FISH and PCR techniques and even 1-2 weeks for cytogenetics . Our results confirmed the current practice that chromosome analysis required a median of 7 d (minimum 2 d, maximum 19 d) and RT-PCR, 7 d (minimum 2 d, maximum 13 d) (Table 3). Although RT-PCR might require 2-3 d, we realized that RT-PCR was being performed on a weekly basis due to the limited numbers of well-trained technicians and PCR machines, which resulted in the disappointingly long TAT of RT-PCR.
The present study showed that induction therapy required a median of 0 d because most patients started the therapy on the same day that the BM study was conducted. The decision to start therapy was made depending mainly on the morphology, cytochemical reaction, and/or immunophenotype of the leukemic blasts. In practice, hematologists tend to start induction therapy with an unknown state of t(15;17) or
The current practice seems too slow and time consuming for routine diagnostic applications and needs to be improved in the detection of the characteristic oncogene or oncoprotein. To improve the clinical and laboratory flow, it might be necessary to introduce a much faster technique that can be performed more easily and without special laboratory facilities, as well as a more meticulous management of skills to adjust and prioritize the laboratory processes. A promising new method called the PML-RARA immunobead assay, which adopts a faster and easier flow cytometric technique and immunobead-based detection of the fusion protein, has shown fully concordant results with RT-PCR . We herein highlight the continued requirement for faster assays to be made available for routine laboratory use as soon as possible.
In summary, our study showed that the results confirming the presence of t(15:17) or