Analysis of factors affecting hemorrhagic diathesis and overall survival in patients with acute promyelocytic leukemia

BACKGROUND/AIMS: This study investigated whether patients with acute promyelocytic leukemia (APL) truly fulfill the diagnostic criteria of overt disseminated intravascular coagulation (DIC), as proposed by the International Society on Thrombosis and Haemostasis (ISTH) and the Korean Society on Thrombosis and Hemostasis (KSTH), and analyzed which component of the criteria most contributes to bleeding diathesis. METHODS: A single-center retrospective analysis was conducted on newly diagnosed APL patients between January 1995 and May 2012. RESULTS: A total of 46 newly diagnosed APL patients were analyzed. Of these, 27 patients (58.7%) showed initial bleeding. The median number of points per patient fulfilling the diagnostic criteria of overt DIC by the ISTH and the KSTH was 5 (range, 1 to 7) and 3 (range, 1 to 4), respectively. At diagnosis of APL, 22 patients (47.8%) fulfilled the overt DIC diagnostic criteria by either the ISTH or KSTH. In multivariate analysis of the ISTH or KSTH diagnostic criteria for overt DIC, the initial fibrinogen level was the only statistically significant factor associated with initial bleeding (p = 0.035), but it was not associated with overall survival (OS). CONCLUSIONS: Initial fibrinogen level is associated with initial presentation of bleeding of APL patients, but does not affect OS.

Differential Blast Counts Obtained by Automated Blood Cell Analyzers / 대한진단검사의학회지

BACKGROUND: Automated blood cell analyzers often read leukemic blasts as normal cells. In this study, we evaluated the 5-part differential patterns of blasts using automated analyzers to determine if they can differentiate among blast types. METHODS: Blood samples containing 10% or more blasts were collected from patients with acute leukemia (N=175). The 5-part differential count was conducted using DxH 800 (Beckman Coulter, USA) and XE-2100 analyzers (Sysmex Co., Japan), and the results were compared with manual differential counts, which was used as a reference method. RESULTS: The DxH 800 reported the 5-part white blood cell differential count in 98.9% of the cases. The XE-2100 provided an invalid automated differential count in 72% of the cases. Both analyzers counted most lymphoblasts as lymphocytes and most myeloblasts as monocytes. In 11 cases, the DxH 800 reported a 5-part differential count without a blast flag. CONCLUSIONS: Some automated analyzers are able to recognize and count blasts according to their characteristic cell types. Therefore, complete blood counts obtained automatically can provide valuable data for making provisional decisions regarding the lineage of leukemia cells before further investigation.

[Effects of clinical, hematological and immuno-phenotyping factors on prognosis of acute pro myelocytic leukemia]

Acute Promyelocytic Leukemia, APL, belongs to the group of acute myeloid leukemias. It is distinguished from other types of leukemia by distinct cell morphology, immuno-phenotyping characteristics, coagulopathy and different treatment modalities. The aim of this study was evaluation of the effects of cytologic, clinical and biologic factors specially CD34 expression in determining prognosis in patients with APL. In a descriptive retrospective analysis files of 60 patients with APL were reviewed and data statistically analyzed using SPSS soft ware with Chi Square and T- test. Complete remission and disease free survival [DFS] had no significant correlation with age, sex, WBC, Hemoglobin level, platelet count, purpura, CD34 status, and percentage of blasts in the bone marrow. There was no statistically significant correlation between CD34 expression with morphology, age, sex, WBC, platelet count, percentage of BM blasts and purpura. Cases with CD34 expression had severe anemia, [Hemoglobin=5.8 +/- 1.08], in comparison with patients with CD34 negative APL, [p=0.02]. Results of our study were not concordant with the literature, as recognized prognostic factors had no significant effect on the prognosis of our patients; therefore it is logical to believe that factors influencing the prognosis of APL in Iranian patients may be different. Failure in obtaining complete remission in all 4 patients with CD34+ APL indicates that presence of CD34+ may have been the cause of poor prognosis in these patients. Further studies are necessary to confirm this observation

Haematologic parameters in acute promyelocytic leukemia patients treated with ALL trans- retinoic acid

Acute Promyelocytic Leukemia [APL] is commonly associated with disseminated intravascular coagulation [DIC] and early correction of coagulopathy is of vital importance. All Trans-Retinoic Acid [ATRA] is considered to be the drug of choice in the treatment of APL. The work was conducted to: 1- Identify patients with APL who show laboratory evidence of DIC. 2- Study the serial changes in haemostatic parameters in APL patients treated with ATRA and to compare their results with those treated with conventional chemotherapy without ATRA. In this prospective study [from October 2003 to October 2005], 44 newly diagnosed, untreated APL patients were included. ATRA plus chemotherapy - treated patients were 24 while 17 patients were treated with chemotherapy other than ATRA. For each patient, a full clinical evaluation was done and hematological investigations were accomplished at time of diagnosis and repeated on day 3 and 7 of therapy. Diagnosis of DIC was based on finding a positive D- dimer test with hypofibrinogenaemia with or without pathologically prolonged [PT and/or APTT]. In 44 newly diagnosed, untreated APL patients studied, the age ranged between 6-81 years with a median of 27 years. Male to female ratio was 1.3:1. Before treatment all patients had anemia, thrombocytopenia, and elevated level of D - dimer. DIC was present in all patients at time of diagnosis. All parameters that showed abnormal level at time of diagnosis had returned to normality within one week in ATRA treated group, indicating that DIC has essentially resolved. By contrast, those parameters remained abnormal even on day 7 in the chemotherapy treated group, indicating that DIC was ongoing. ATRA therapy in APL patients is associated with rapid improvement of coagulopathy therefore, it is justified to be used from day one of the treatment

Treatment of acute promyelocytic leukemia: A single institution experience / Tratamiento de la leucemia promielocítica aguda: Experiencia de una sola institución

The results of the treatment of 14 patients with promyelocytic leukemia (PML) treated with all trans-retinoic acid (ATRA), combined chemotherapy (CT) and prophylactic prednisone are reported; the median age was 30 years (range 7 - 49). A complete remission (CR) was obtained in 13 / 14 patients (93%). All patients were given ATRA fully as outpatients; the CR was achieved after the administration of ATRA in five patients, whereas in the remaining eight, CT was required to achieve it. There were no instances of the ATRA syndrome. One patient relapsed with a PML/RAR-a negative PML 575 days after achieving the CR, failed to respond again to ATRA and died. The median overall (OS) and disease free survival (DFS) has not been reached, being above 4,000 days, whereas the 12-month DFS was 93%, the three and five years DFS being 85%. The treatment employed differs from others in: Oral prednisone is used prophylactically, ATRA is given on an outpatient basis and adriamycin is used instead of other anthracyclines. The results are similar to those obtained in other centers worldwide and it is possible that the prophylactic administration of prednisone precluded the development of the full-blown ATRA syndrome in this group of patients.

Se informan los resultados del tratamiento en una sola institución de 14 pacientes con leucemia aguda promielocítica (LAPM) en quienes se empleó la combinación de ácido holotrans-retinoico (ATRA) quimioterapia combinada y prednisona profiláctica. La mediana de edad fue de 30 años (rango 7-49). Se obtuvo remisión completa (hematológica y molecular) (RC) en 13 pacientes (93%); a todos los pacientes se les administró el ATRA de manera ambulatoria. La RC se obtuvo con el ATRA en cinco pacientes; en los demás la RC se obtuvo después de habérseles administrado la quimioterapia con citarabina/adriamicina. No hubo ningún caso de síndrome de ATRA. Un paciente recayó con una LAPM PML/ RAR-a negativa, 575 días después de haber logrado la RC y falleció. Otro paciente recayó 20 meses después de haber logrado la RC y fue rescatado con el mismo esquema de tratamiento; permanece en segunda remisión molecular por más de seis años. La mediana de supervivencia (SV), tanto global como libre de recaídas de todo el grupo, no se ha alcanzado y es mayor de 4,000 días, en tanto que la SV a 12 meses fue de 93% y a tres y cinco años de 85%. El esquema de tratamiento usado difiere de otros en que se usa prednisona oral, se administra el ATRA de manera ambulatoria y se usa adriamicina y no otras antracidinas; los resultados son similares a los obtenidos con otros esquemas parecidos en otros sitios del mundo; es posible que el uso profiláctico de prednisona haya eliminado la ocurrencia del síndrome de ATRA.

Clinics hematologic study of adult AML, A retrospective analysis

This retrospective study was carried out from the cases of adult acute myeloid leukemia diagnosed at Haematology Department of King Edward Medical College, Lahore, over a period of five years, from 1994-1999. M1 was the commonest subtype. Common presenting features were anemia, bleeding and infections along with some uncommon symptoms in individual cases

Trastornos de la hemostasia en la leucemia promielocitica aguda

Se estudio la hemostasia en 20 pacientes con leucemia promielocitica aguda (LPA), antes del tratamiento, durante la induccion de la remision y despues de obtener la remision completa (RC). Se detecto coagulacion intravascular diseminada (CID) en 14 casos, el 71 por ciento de ellos en el momento del diagnostico. Se encontro una mayor mortalidad en las primeras semanas de evolucion, frecuencia de episodios hemorragicas, asi como un menor porcentaje de RC en enfermos con CID. El tratamiento con heparina se utilizo en 8 pacientes, con buenos resultados en 6 de ellos (75 por ciento), en 5 de estos casos se uso conjuntamente el acido retinoico en trans (ART). En el 83,3 por ciento de los pacientes con CID tratados con ART se logro la correccion de la coagulopatia entre 1 y 2 semanas. En el 10 por ciento de los casos se encontraron evidencias clinicas de trombosis. Los resultados obtenidos demuestran que la CID ocupa un lugar central en los trastornos de la hemostasia en la LPA, tiene una repercusion importante sobre el desarrollo clinico de la enfermedad y puede lograrse su rapida eliminacion con el tratamiento con ART en la mayoria de los pacientes

All trans retinoic acid.

ATRA is extremely effective for inducing clinical remission in APML. The presence of PML/RAR-alpha fusion gene produced as a result of the unique chromosomal translocation in APML is a marker of the sensitivity to ATRA therapy. Further research is needed to elucidate the mechanisms by which the development of the fusion protein in APML leads to the arrest of myeloid differentiation. ATRA leads to rapid resolution of the coagulopathy associated with APML. There is a major clinical benefit since coagulopathy often causes early fatal hemorrhage. The effectiveness of ATRA in APML can serve as a paradigm for the use of differentiation therapy in human malignancies.

Cytochemical stainings in acute promyelocytic leukemia: chloroacetate esterase reaction as a prognostic index.

Cytochemical studies including peroxidase, sudan black B and esterases were used for staining peripheral blood and bone marrow smears from 42 patients with acute promyelocytic leukemia. The most sensitive methods were sudan black B (mean 98%, range 81-100%) and peroxidase (mean 92% range 70-100%). Naphthol AS-D chloroacetate esterase activity was less sensitive and was positive in only 49.4 per cent (range 2-100%). All of the population of leukemic cells contained less than 3 per cent of alpha-naphthyl acetate esterase staining. For stability tests of the storage specimens compared to fresh stains, there was no difference in naphthol AS-D chloroacetate esterase (mean 45% vs 49% P greater than 0.7) and sudan black B (mean 74% vs 98% P greater than 0.3), but the enzyme activity was significantly decreased in peroxidase staining (mean 42% vs 92% P greater than 0.05). When the patients were divided into 2 groups according to the degree of AS-D chloroacetate esterase activity, those with lower activity had a higher number of white blood cells, promyelocytes and shorter survival compared to those with higher activity. Therefore, naphthol AS-D chloroacetate esterase may be useful as a prognostic index.