1/15. A variant form of acute promyelocytic leukemia with marked myelofibrosis.We describe a variant form, French-American-British (FAB) M3v, of acute promyelocytic leukemia (APL; FAB M3) with atypical morphocytochemical features, immature antigens (CD34 and HLA-DR) and marked myelofibrosis (MF). Usual APL cells do not express CD34 or hla-dr antigens. MF may be more frequently observed in patients with M3v expressing CD34 and hla-dr antigens than in patients with M3 lacking these antigens. Despite marked MF, recovery from the hypoplastic phase in the case we described was not delayed after remission induction chemotherapy consisting of enocitabine, 200 mg/mi2 intravenously; 6-mercaptopurine, 70 mg/m2 orally for 10 days; daunorubicin 40 mg/m2 intravenously for 4 days; and all-trans retinoic acid 45 mg/M2 orally between days 20 and 33. The promyelocytic leukemia-retinoic-acid receptor (PML-RAR) alpha fusion transcript, according to reverse transcriptase-polymerase chain reaction (RT-PCR), became negative in the bone marrow after the first course of consolidation chemotherapy. Autologous peripheral blood stem cell transplantation (autoPBSCT) was carried out after 3 courses of consolidation chemotherapy. There were no specific complications based on MF throughout the clinical course, including engraftment in autoPBSCT. The patient has been without MF and in molecular remission, defined as disappearance of the PML-RAR alpha fusion transcript according to RT-PCR, for 21 months. Longer follow-up will clarify the effects of autoPBSCT on prognosis in APL with MF.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/15. clonal evolution of blasts in an elderly patient with CD56( ) relapsed acute promyelocytic leukemia.We describe an elderly patient with acute promyelocytic leukemia (APL), whose leukemic cells expressed CD56 antigen at relapse but not at diagnosis. Chromosome analysis revealed that blasts with t(8;15;17)(q24.1;q22;q11.2) increased from 4 of 20 cells (20%) at first relapse to 10 of 14 cells (71.4%) at second relapse. In addition, the positivity for CD56 expression on blasts judged by flow cytometric analysis using CD45 blast gating was also increased from 14.2% at first relapse to 75% at second relapse. Although conventional chemotherapy was performed for the initial disease and the first relapse, relapse developed again. Therefore, three courses of intensive postremission chemotherapy including concurrent administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) with cytarabine were performed after achievement of complete remission (CR) by the treatment with all-trans-retinoic acid (ATRA). Although PML-RARalpha mRNA was not detectable by reverse transcription polymerase chain reaction (RT-PCR), a third relapse occurred. This case demonstrated clonal evolution from a CD56(-) to a CD56( ) blast population and provided further support for the suggestion that CD56 expression might be an unfavorable prognostic factor in t(15;17) APL.- - - - - - - - - - ranking = 0.25keywords = antigen (Clic here for more details about this article) |
3/15. Automated analysis of differentiation-induced leukemic cells during all-trans retinoic Acid therapy of acute promyelocytic leukemia.During differentiation-induction therapy of acute promyelocytic leukemia (APL) patients with all-trans retinoic acid (ATRA), a variety of APL-derived bizarre granulocytic cells appear in the peripheral blood. To evaluate the differentiation induction of leukemic cells, we have developed a new scattergram analyzing program with an automated hematology analyzer and compared the data with the flow cytometry measuring the expression of differentiation-associated cell surface antigens, cd11b and CD16. We used the fluorescence intensity and side scatter as parameters of granulocytic maturation in the analysis with the automated hematology analyzer. The analysis of 2 ATRA-treated APL patients and in vitro study using hl-60 cells demonstrated that the levels of fluorescence intensity and side scatter decreased as accompanied with granulocytic maturation, and these changes were parallel with the results of flow cytometry. Our automated scattergram analysis of cell differentiation will contribute to general, objective, and real-time evaluation of differentiation-induction therapy of APL with ATRA.- - - - - - - - - - ranking = 0.25keywords = antigen (Clic here for more details about this article) |
4/15. Usefulness of RA and RO isoforms of common leukocyte antigen (CD45) for early distinction between normal and abnormal promyelocytes.Normal promyelocytes express CD45RO, while acute promyelocytic leukemia (APL) blasts express CD45RA, both isoforms of common leukocyte antigen with mutually exclusive expression. Here we report a patient with accumulation of promyelocytes in the bone marrow and the diagnostic strategy is described along with the ability to quickly discriminate between normal and abnormal cells using the flow cytometric detection of expression of RA/RO isoforms of CD45.- - - - - - - - - - ranking = 1.25keywords = antigen (Clic here for more details about this article) |
5/15. Cytogenetic and molecular analysis of an unusual case of acute promyelocytic leukemia with a t(15;17;17)(q22;q23;q21).We present a 52-year-old female with a clinical history of acute myelocytic leukemia, probable acute promyelocytic leukemia (APL). flow cytometry results were somewhat unusual. Specifically, the promyelocytic population showed partial positivity for antigens not usually expressed in APL (HLA-DR and CD117). The interpretation of these results was that the abnormal population contained a proportion of very early promyeolocytes that had not completely lost all their "precursor" antigens. cytogenetic analysis of a bone marrow aspirate showed a t(15:17;17)(q22;q23;q21) in all cells analyzed. fluorescence in situ hybridization (FISH) analysis using the PML-RARA dna probe showed a positive signal pattern (fusion) in 100% of 200 total interphase and metaphase cells examined, confirming the presence of the PML-RARA rearrangement. Multicolor FISH, which produces 24 colors to differentiate all chromosomes in a single hybridization, was applied. This study confirmed the cytogenetic interpretation of the rearrangement. No material from any other chromosome was detected on the second smaller derivative chromosome 17. Additional studies using the RARA(17q21) break-apart dna FISH probe showed that 17q21 (RARA) was not rearranged on the derivative chromosome 17 that received the q22-->qter segment from chromosome 15. The RARA locus on the smaller derivative 17 was the allele involved in the fusion in this three-way rearrangement. The signal pattern was consistent in 100% of interphase and metaphase cells scored. This unusual t(15;17;17) prompted us to investigate further using reverse-transcription polymerase chain reaction with primers from the 3' and 5' regions of both the RARA and PML loci. These studies showed that the PML-RARA fusion was present, but the complementary fusion RARA-PML, which is usually detectable, was absent. The patient is responding well to standard treatment protocols.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
6/15. Reverse seroconversion of hepatitis b virus infectious status after allogeneic bone marrow transplantation from a carrier donor.A 35-year-old man with acute promyelocytic leukemia received an allogeneic bone marrow transplant (BMT) in second complete remission. The donor was his 18-year-old brother, a chronic hepatitis b virus (HBV) carrier with detectable serum hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis b virus dna (HBV dna). Before BMT, the recipient was immune to HBV, with serum antibody to HBsAg (anti-HBs), antibody to HBeAg (anti-HBe) and normal liver function. Examination of the recipient serum drawn 2 months after BMT revealed reverse seroconversion from anti-HBs/anti-HBe to HBsAg/HBeAg, which remained positive thereafter. Upon reducing cyclosporin 6 months after BMT, acute hepatitis occurred with HBV dna in serum as evidence of active HBV replication; the patient then developed chronic hepatitis which progressed to cirrhosis and hepatic decompensation within 8 months. Transfusion of HBV dna/HBeAg-positive bone marrow is thus harmful even when the recipient has anti-HBs prior to BMT.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
7/15. Solid tumors subsequent to arsenic trioxide treatment for acute promyelocytic leukemia.arsenic trioxide (As(2)O(3)) is highly efficacious for acute promyelocytic leukemia (APL). Environmental arsenic exposure predisposes to malignancies, but the risk for therapeutic arsenic is undefined. Three APL patients (de novo, 2; therapy-related, 1) in a cohort of 59 cases given oral-As(2)O(3) for induction and maintenance treatment developed secondary cancers (nasopharyngeal carcinoma, 2; colonic adenocarcinoma, 1) at 16, 36 and 55 months post-As(2)O(3) therapy. Retrospective analysis of biomarkers (Epstein Barr virus serology and quantification, carcinoembryonic antigen) showed the potential presence of cancers before or shortly after As(2)O(3) therapy, suggesting that As(2)O(3) had not initiated these malignancies. Compared against matched background population, there was an increased risk of second cancer (p=0.012, standard incidence ratio=6.5; 95% confidence interval=1.4-19.0).- - - - - - - - - - ranking = 0.25keywords = antigen (Clic here for more details about this article) |
8/15. invasive pulmonary aspergillosis: role of early diagnosis and surgical treatment in patients with acute leukemia.BACKGROUND: aspergillus is a ubiquitous soil-dwelling fungus known to cause significant pulmonary infection in immunocompromised patients. The incidence of aspergillosis has increased during the past two decades and is a frequently lethal complication of acute leukemia patients that occurs following both chemotherapy and bone marrow transplantation. The diagnosis of invasive pulmonary aspergillosis (IPA) according to the criteria that are established by European Organization for the research and Treatment of Cancer and mycoses Study Group raise difficulties in severely ill patients. Despite established improvements in field of diagnosis (galactomannan antigen, quantitative PCR, real-time PCR for aspergillus spp., and findings of computed tomography) and treatment with new antifungals, it is still a major problem in patients with acute leukemia. However, prompt and effective treatment of IPA is crucial because most patients will need subsequent chemotherapy for underlying hematologic disease as soon as possible. CASE PRESENTATION: We report a 33-year-old male patient with acute promyelocytic leukemia diagnosed in 1993 that developed invasive pulmonary aspergillosis due to A. flavus at relapse in 2003. The patient was successfully treated with liposomal amphotericin b and underwent surgical pulmonary resection. The operative course was uneventful. CONCLUSION: This report emphasizes the clinical picture, applicability of recent advances in diagnostic and therapeutic approaches for IPA. For early identification of a patient infected with IPA, a high index of suspicion and careful clinical and radiological examinations with serial screening for galactomannan should be established. If aspergillosis is suspected, anti-aspergillosis drug should be administered immediately, and if a unique pulmonary lesion remains, surgical resection should be considered to prevent reactivation during consecutive chemotherapy courses and to improve the outcome.- - - - - - - - - - ranking = 0.25keywords = antigen (Clic here for more details about this article) |
9/15. RARA and PML gene rearrangements in acute promyelocytic leukemia with complex translocations and atypical features.The translocation t(15;17) associated with acute promyelocytic leukemia (APL) results in fusion of the retinoic acid receptor alpha (RARA) gene on chromosome 17 with the putative transcription factor gene, PML, on chromosome 15. We report three cases of APL with complex cytogenetic translocations and five cases with atypical phenotypic features with rearrangements within or adjacent to the second intron of the RARA gene. Two patients demonstrated three-way translocations involving chromosomes 3, 15, and 17, but with differing breakpoints on the short arm of chromosome 3. A third patient developed a complex karyotype at the time of third relapse, but with no change in RARA and PML gene rearrangement pattern. Three patients had normal karyotypes; however, only small numbers of cells could be analyzed. One patient's leukemic cells expressed the T-cell-associated antigen CD2 and revealed T-cell receptor beta and gamma gene rearrangements. The localization of breakpoints to the second intron of the RARA gene in cytogenetically and phenotypically atypical cases provides additional support for a requisite role of the PML/RARA fusion gene in the pathogenesis of APL.- - - - - - - - - - ranking = 0.25keywords = antigen (Clic here for more details about this article) |
10/15. Functional characteristics of mature granulocytes in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid.All-trans retinoic acid (ATRA) is a differentiating agent that has been successfully used in the treatment of patients with acute promyelocytic leukemia (APL). Functional properties of peripheral blood neutrophils from a patient with APL during treatment with ATRA have been studied. Wright stain of patient neutrophils showed hypogranulation and loose nuclear chromatin when compared with normal neutrophils. These cells were of lower density than normal neutrophils and separated on density gradient centrifugation with mononuclear cells. Surface antigen expression by FACS distinguished these cells from lymphocytes. The histograms showed a population of larger cells expressing CD18 and CD11b, distinct from the smaller cells which did not express CD11b. fMLP caused an increase in intracellular calcium (measured spectrophotometrically) that was inhibited by the calcium chelator BAPTA. Actin polymerization following cell activation was measured using NBD-phallacidin staining and FACS. Both IL-8 and fMLP caused rapid increases using F-actin content (2.5-3.0 fold), which were of greater magnitude than generally seen with normal neutrophils. Treatment with BAPTA before activation with fMLP did not blunt the actin responses, despite complete inhibition of an intracellular calcium increase. In summary, neutrophils derives from differentiated APL cells express CD18/CD11b, and exhibit a similar degree of actin polymerization in response to fMLP and IL-8, independent of an increase in intracellular calcium. Although the actin responses are greater than normal neutrophils, most properties are similar, supporting the contention that these cells can protect the host. The exaggerated actin response to inflammatory mediators, however, may play a role in the 'retinoic acid syndrome'.- - - - - - - - - - ranking = 0.25keywords = antigen (Clic here for more details about this article) |
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