Leucemia promielocítica aguda: Resultados del protocolo terapéutico LPA2000, Programa Nacional de Cáncer del Adulto (PANDA), Ministerio de Salud, Chile / Acute promyelocytic leukemia: Results of the Chilean protocol LPA2000

Background: The current recommendations for treatment of patients with newly diagnosed acute promyelocytic leukemia (APL) include all-trans-retinoic acid (ATRA) and anthracycline based chemotherapy. Aim: To evaluate the results of the Chilean protocol following the LPA99 regimen of the Spanish PETHEMA group, except for the replacement of Idarubicin by Daunorubicin. Patients and Methods: Induction consisted of Daunorubicin 45 mg/m² on days 2, 4, 6 and 8 plus ATRA 45 mg/m² daily until complete remission. Patients in complete remission (CR) received three monthly chemotherapy courses: Daunorubicin 45 mg/m²/d/4days i.v. and ATRA 45 mg/m²/d/15 days p.o. (course no. 1); Mitoxantrone 10 mg/m²/d/5 days i.v. and ATRA 45 mg/m²/d/15 days p.o. (course no. 2); Daunorubicin 60 mg/m²/d/ day 1 i.v. in the low risk group, and 1 and 2 in the intermediate-high risk groups and ATRA 45 mg/m²/d/15 days p.o. (course no. 3). Maintenance therapy consisted of mercaptopurine 90 mg/m²/d p.o., methotrexate 15 mg/m²/wk p.o. and, ATRA intermittently, 45 mg/m²/d p.o. for 15 days every three months. Results: Between January 2000 and December 2005, 56 patients with newly diagnosed APL from 10 centers were enrolled. A total of 46 patients achieved CR (85%), 8 (15%) died of early complications, seven patients relapsed, with a 16% relapse risk at three years. The 5-year Kaplan-Meier estimates of overall survival and relapse-free survival were 64% and 84% respectively. Conclusions: These data indicate that this protocol has a good antileukemic effect but further reduction of early death and relapse, especially in the high risk group is needed.

Primer caso de leucemia mieloide aguda tratado en Cuba con altas dosis de antraciclinas en la inducción / First case of acute myeloid leukemia treated in Cuba using high doses of anthracycline in induction

La leucemia mieloide aguda abarca un heterógeneo espectro de enfermedades, de naturaleza maligna y clonal, que representan un reto formidable para la medicina moderna. Con la excepción de la leucemia promielocítica, los resultados terapéuticos alcanzados continúan siendo desalentadores. Recientemente han surgido datos que demuestran mejores resultados con el uso de altas dosis de antraciclinas en la inducción. Se presentó el primer caso en Cuba, en cuya inducción se utilizó la rubidomicina a 100 mg/m² por 3 d, más el arabinósido de citosina a 100 mg/m² por 7 d, ambos en infusión endovenosa continua. La evolución clínica es satisfactoria hasta el momento. Se revisó brevemente la literatura médica al respecto...

The acute myeloid leukemia includes an heterogeneous spectrum of diseases of malignant and clonal origin representing a challenge of the current medicine. With the exception of the pro-myelocytic, the achieved therapeutical results continue being discouraging. Recently are available data demonstrating better results with the use of high doses of anthracycline in the induction. This is the first case in Cuba where in induction it was used the 100 mg/m² rubidomicin plus 100 mg/m2 for three days plus 100 mg/m² arabinoside for seven days, both in continuous intravenous infusion. The clinical course is satisfactory until now. Authors made a brief review of medical literature in this respect...

Outcomes of a Modified CALGB 19802 Regimen in Adult Acute Lymphoblastic Leukemia

We analyzed the efficacy and toxicity of a modified Cancer and Leukemia Group B (CALGB) 19802 regimen in adult acute lymphoblastic leukemia (ALL). From February 2002 to August 2005, 25 adults with untreated ALL were enrolled in the study. Compared to the original regimen, the modified CALGB 19802 regimen consisted of a 4-drug induction (cyclophosphamide, daunorubicin, vincristine, and prednisone) instead of a 5-drug induction (L-asparaginase was added to the previous regimen). This was followed by high-dose methotrexate (1,000 mg/m(2)X3 days) and cytarabine (2,000 mg/m(2)X4 days) for the consolidation cycles. High-dose systemic and intrathecal methotrexate was given for central nervous system prophylaxis. Twentythree patients (92%) achieved a complete remission (CR), and two patients (8%) had refractory disease. With a median follow-up of 21.5 months, 10 patients (40%) were alive and continued to be in CR. The 3-yr probability of an event-free survival and the overall survival were 39.0% and 47.4%, respectively. Treatment related mortality and major grade 3 to 4 neurotoxicity occurred in 1 patient and 3 patients, respectively. The modified CALGB 19802 regimen demonstrated a high remission rate and a favorable survival rate.

Liposomal daunorubicin and dexamethasone as a treatment for multiple myeloma: the DD Protocol

CONTEXTO E OBJETIVO: A daunorrubicina lipossomal tem sido usada no tratamento em várias doenças hematológicas malignas, incluindo mieloma múltiplo (MM). O objetivo deste estudo foi avaliar a eficácia, efeitos colaterais e toxicidade da daunorrubicina lipossomal and dexametasona no Protocolo DD. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, realizado nos hospitais Sírio Libanês, São Camilo, Brasil e no Hospital Alemão Oswaldo Cruz. MÉTODOS: 20 pacientes com MM ativo receberam daunoxome (25-30 mg/m²/dia) por três dias consecutivos, mensal, por quatro meses (total de quatro ciclos), e dexametasona, 10 mg a cada seis horas por quatro dias consecutivos (dia 1 - 4, 9 - 12 e 17 - 20), também mensal. RESULTADOS: A mediana entre o diagnóstico e o início do protocolo DD foi de 13 meses. Quinze pacientes receberam alguma quimioterapia anterior ao protocolo DD. Uma redução maior que 50% do pico monoclonal sérico foi observada em seis paciente após o primeiro ciclo do DD (30%), em seis pacientes após o segundo ciclo (30%), em quatro pacientes após o terceiro ciclo (20%) e em quatro pacientes não houve redução (20%). No início do protocolo, 17 pacientes (85%) apresentavam anemia e em 12 destes pacientes (70%) a anemia foi corrigida. Doença progressiva foi observada em três pacientes (15%), um apresentava resposta mínima, quatro pacientes (20%) apresentaram resposta parcial e 12 (60%) apresentaram resposta completa. A toxicidade hematológica foi aceitável.Toxicidade em trato gastrointestinal foi leve, consistindo em náusea (10%) e anorexia (15%), sem episódios de vômito. CONCLUSÃO: Este tratamento apresentou uma baixa toxicidade, uma boa taxa de resposta e pode ser usado previamente ao transplante de medula óssea autogênico.

Control of acute myeloid leukemia morbidity in northwest Iran.

BACKGROUND: To investigate protocols of remission induction therapy for prevention of morbidity of acute myeloid leukemia. MATERIALS AND METHODS: The responses of 150 patients to "2+5" and "3+7" protocols during 1996-2003 were assessed and analyzed with the Chi-Square method. RESULTS: Complete remission was observed in 30% of cases treated with 2 days of daunorubicin and 5 days of cytarabine (2+5 regimen). Remission was increased to 52.5% when patients were treated with 3+7 regimens with the same drugs. Partial remission resulted in 25 and 10 percent of cases, respectively. CONCLUSION: As in previous studies the 3+7 regimen was demonstrated to be more effective than the 2+5 regimen in our hospital (p=0.0009).

Outcome of acute myeloid leukaemia in adults: a retrospective analysis.

BACKGROUND: There are little data from India on the management of acute myeloid leukaemia. With better understanding of the biology of the disease, and routine use of high-dose cytarabine as post-remission therapy with or without haematopoietic blood stem cell transplantation (HSCT), the results have improved in the past two decades. We analysed our results in a cohort of recently treated patients. METHODS: A total of 166 newly diagnosed patients with AML (excluding acute promyelocytic leukaemia), 15-60 years of age were treated with daunorubicin (60 mg/m2/day x3 days) or idarubicin (12 mg/m2/day x3 days) with cytarabine (100 mg/m2/day continuous i.v. infusion x7 days) induction chemotherapy. Post-remission therapy included 2 cycles of high-dose cytarabine (15-18 g/m2) followed by monthly cycles of outpatient maintenance chemotherapy x4 cycles, consisting of daunorubicin (45 mg/m2 i.v. x1 day and cytarabine 100 mg/ m2 s.c. twice daily x5 days). Six patients in remission received sibling donor allogeneic HSCT. RESULTS: Morphological complete remission was achieved in 69.9% of the patients. Resistant disease after induction chemotherapy was seen in 14.6% and early mortality occurred in 16%. Relapse-free survival and event-free survival at a median of 36 months was 34% and 22%, respectively. Relapse occurred in 43.9%. The median duration of remission was 12 months. CONCLUSIONS: Our results conform to the published literature from larger cooperative studies from the West. Currently available cytotoxic drugs are unlikely to improve the results any further.

All-transretinoic acid and chemotherapy in the treatment of acute promyelocytic leukemia.

BACKGROUND: All-transretinoic acid (ATRA) and chemotherapy has improved complete remission rates and disease free survival in acute promyelocytic leukemia (APL). There is scanty data from Middle East. AIM: To determine the efficacy of ATRA and multi-agent combination chemotherapy in treatment of APL in a single Centre in Kuwait. SET-UPS AND DESIGN: Tertiary cancer centre, retrospective study. METHODS AND MATERIAL: All newly diagnosed APL patients were treated with oral ATRA 45 mg/m2 daily until complete remission (CR), intravenous daunorubicin 50 mg/m2 on days 1,3 and 5, cytosine arabinoside 100 mg/m2 12 hrly on days 1 through 10 and etoposide 100 mg/m2 on days 1 through 5. Post remission three courses of intensive consolidation chemotherapy were administered. Since October 1999, maintenance chemotherapy consisting of oral 6 mercaptopurine 9 mg/m2 daily, methotrexate 15 mg/m2 weekly and ATRA 45 mg/m2 for 2 weeks every three months was added. Complete remission rates and duration, relapse rate and toxicity were studied. RESULTS: 22 of 24 evaluable patients (91.6%) achieved CR. The median duration of remission was 13 months (range 2-55 months). Three patients (12.5%) relapsed. Two patients (8.3%) developed retinoic acid syndrome and responded to dexamethasone. Five patients (20.8%) died one each of refractory disease, during remission induction and of relapse. Two patients died while in remission. CONCLUSION: ATRA and combination chemotherapy results in high complete remission rates and low relapse rate in newly diagnosed APL. Maintenance therapy may be useful in preventing relapses.

Chromosomal rearrangement in Down syndrome with acute myeloid leukemia.

The incidence of acute leukemia in children with Down syndrome (DS) is high as compared to general population. Recent findings have demonstrated that DS children with acute myeloid leukemia (AML) have the highest event free survival rates with high dose cytosine arabinoside (Ara-C). We present 3 year-old DS female child with AML-M5, whose chromosomal analysis revealed constitutional t(21;21) alongwith del(5)(q31q33) and a unique translocation t(16;20)(q13;q12). After chemotherapy, child achieved complete clinical remission. Karyotype analysis of remission marrow showed disappearance of abnormal clone of der(20) t(16;20)(q13;q12), del(5q) indicating cytogenetic remission too. This case alongwith supportive literature indicate that pediatric DS-AML is a distinct biologic sub-group differs from that of non-DS-AML with respect to chemosensitivity.

Leucemia mieloide aguda del adulto: resultado del protocolo nacional de drogas antineoplásica: Hospital del Salvador 1990-1998 / Acute myeloid leukemia in the adult: results of the national antineoplastic drug protocol (Panda) at Hospital del Salvador, Chile

Background: The incidence of acute myeloid leukemia is 3 cases per 100.000 inhabitants/year and its five years event free survival is 15 to 20 percent. Since the incorporation of trans retinoic acid, event free survival of M3 acute myeloid leukemia is 80 percent. Aim: To report the results of acute myeloid leukemia treatment at the Hospital del Salvador, between 1990 and 1998. Patients and methods: The medical records of 117 patients (66 female, mean age 48.2 years), treated between 1990 and 1998 using PANDA protocol, were retrospectively reviewed. Immunophenotyping was done in 69 patients and cytogenetic studies were done in 65. Results: Sixteen percent of patients had M3 acute myeloid leukemia. The most frequent phenotype was the association of DR, CD34 plus a panmyeloid marker. DR and CD34 were negative in seven of nine patients with M3 acute myeloid leukemia. Cariotype was abnormal in 78 percent of patients. Complete remission was achieved in 65 percent of cases with a 13 percent of failures. Early mortality was 21.3 percent and decreased to 6.1 percent in the last three years. Infections and coagulation disorders were the main causes of death. Mean survival was 10.5 months. Five years event free survival was 11 percent. In M3 acute myeloid leukemia, the figure is 50 percent. Conclusions: Treatment results are less effective than protocols that consider more aggressive chemotherapeutic protocols or bone marrow transplantation. The reduction in early mortality is due to a better management of febrile neutropenia

Granulocyte macrophage--colony stimulating factor (GM-CSF) as adjunct in induction therapy of acute myeloid leukemia.

Use of growth factors (G-CSF/GM-CSF) as adjunct in induction therapy of AML is controversial. Possible stimulation of leukemia cell clones has been the major cause of concern. We treated 50 cases of AML with GM-CSF as an adjunct during induction therapy. 35 patients (70%) achieved complete remission out of which 13 patients relapsed at a median relapse period of 15 months. Average duration of neutropenia was 10.5 days. (15 days in the control) Febrile episodes were fewer and antibiotic support was required for an average period of only 7.6 days (16.9 days in the control). The benefits including the economic analysis of the role of GM-CSF in this setting is discussed.

Esquemas de quimioterapia y bacteriemias en pacientes adultos con leucemia aguda / Chemotherapy schedules and bacteremias in adult patients with acute leukemia

En un estudio efectuado para evaluar la utilidad de la profilaxis con fluoroquinolonas en pacientes neutropénicos afebriles, se encontró una asociación inesperada entre el esquema de poliquimioterapia utilizado y la posterior documentación de bacteriemias durante los episodios de neutropenia y fiebre. Se analizaron 25 episodios de neutropenia febril secundaria a quimioterapia antileucémica. Los pacientes recibieron etoposide y mitoxantrona o bien citarabina - en dosis estándar, intermedia o alta - asociada a daunomicina o mitoxantrona. El análisis de los datos microbiológicos demostró una mayor incidência de bacteriemias con el uso combinado de antraciclinas y citarabina en dosis intermedia o alta en comparación con la administración de etoposide y mitoxantrona (p = 0,000387). Ambos grupos de pacientes desarrollaron una neutropenia igualmente veloz y severa con una mucositis digestiva equivalente. El esquema de poliquimioterapia fue el único dato que se asoció con la aparición o no de bacteriemias en el episodio de neutropenia febril subsiguiente. Se concluye en que otros efectos - además de la aplasia medular y la mucositis digestiva - podrían ser relevantes en la susceptibilidad a las infecciones que originan los citostáticos.

Treatment of acute lymphoblastic leukaemia in adults with modified BFM regimen.

Sixty-two adults with acute lymphoblastic leukaemia (ALL) were treated with a modified BFM regimen. Forty-two (70%) achieved complete remission (CR). Twenty-one percent of all evaluable patients and 32.4 percent of complete responders are in continuous complete remission (CCR) at a median follow-up of 41 months (range 24-81 months). Long-term survival was better in T- ALL (47.1%) when compared to precursor-B ALL (4.8%) (P < 0.04).

Prognostic significance of myeloperoxidase containing blast cells in acute myelogenous leukaemia.

Fifty three newly diagnosed patients of de novo acute myelogenous leukaemia (AML) received treatment consisting of remission induction with daunorubicin 60 mg/m2 on day one and continuous infusion of cytosine arabinoside 200 mg/m2/day over 24 h from day one to 7. Thereafter patients in complete remission received consolidation chemotherapy with two identical courses. Complete remission (CR) could be achieved in 40 patients (75.5%). Seven patients (13.2%) died with complications during aplasia phase following remission induction therapy while six patients (11.3%) had resistant disease. Twenty seven patients (67.5%) developed relapse while eight patients (15.1%) continue to remain in complete remission ranging from 51 to 68 months (median 62.5). The projected event free survival and disease free survival at 60 months is 15 per cent (SE + 11.9%) and 21 per cent (+6%) respectively. Evaluation of the prognostic significance of pretherapy characteristics showed that infection at presentation and low number of myeloperoxidase (MPO) containing blasts affected the achievement of complete remission adversely on univariate analysis. Similarly age at diagnosis, of more than 45 yr, total leucocyte count of 50,000/cumm or more and low number of MPO containing blasts affected the remission duration (disease free survival) adversely on univariate analysis. On multivariate analysis, MPO positivity of blast cells, remained the only significant independent characteristic. High MPO positivity affected the remission duration favourably (P < 0.01). Patients with high MPO positivity also achieved CR with one induction cycle in 32 out of 40 instances while only 2 out of 5 patients with low MPO positivity, achieved CR with one chemotherapy cycle (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Leucemía mieloide aguda en niños del Hospital Universitario de Caracas (Período 1979-1989) / Acute myeloid leukemia in children at the University Hospital of Caracas (period 1979-1989)

En el Hospital Universitario de Caracas 52 nuevos casos de Laucemia Mieloblástica aguda (LMA) fueron tratados en dos series consecutivas entre 1979-1989. Concomitantemente se intentó correlacionar los hallazgos clínicos y de laboratorio al ingreso, y la respuesta al tratamiento, con los subtipos morfológicos (FAB) de LMA. Serie I (1979-1985): comprendió 37 niños que recibieron principalmente la terapia de inducción con Citosina Arabinosa 100 mg/m2/día, en una infusión continua por 7 días, además de Daunomicina 45 mg/m2/día, en los 3 primeros días del tratamiento. La serie II incluyó solo 15 pacientes tratados en igual forma, excepto por la Citosina Arabinosa que se administró durante 10 días. Los pacientes que alcanzaron remisión en ambas series recibieron luego 5 ciclos con el esquema de COAP como terapia de consolidación. Posteriormente, fueron a un tratamiento de mantenimiento semanal con 6-Thioguanima por 4 días más Citosina Arabinosa el 5to. día durante 24 meses en remisión contínua. el tratamineto de inducción se realizó en 44 niños, dado que 7 murieron durante la fase de inducción en aplasia y otro caso se descartó por Síndrome de Down. La remisión completa fue de 64 por ciento (21/33) en la Serie I y de 36 por ciento (4/11) en la Serie II; observandose en ambas series un 42 por ciento de LMA con un componente monocítico, la mayoría del tipo M4 y 80 por ciento (20/25) de los casos que alcanzaron remisión, presentaban diferenciación mieloide FAB M1-M4. La duración de la remisión fué corta, lo que sugiere fallas en el tratamiento citotócico recayendo el 60 por ciento en los primeros 6 meses. La sobrevida libre de enfermedad fue menor de 20 por ciento al año y de sólo 6 por ciento a los 30 meses, sin diferencias estadísticas significativas en las 2 Series. Se estima que la problemática asistencial crónica de nuestro hospital pudo haber influido en la alta tasa de mortalidad temprana. Esta es la primera casuística de niños con LMA reportada en Venezuela

Comparación de dos esquemas de quimioterapia en la leucemia aguda mieloblástica del adulto: resultados del grupo cooperativo / Non-ablative combined chemotherapy in adults with acute myelogenous leukemia: the INNSZ cooperative group

En este estudio retrospectivo se analizan los resultados del tratamiento de 76 pacientes adultos con leucemia aguda mieloblástica (LAM); 43 fueron tratados con el esquema quimioterápico 7 + 3 (arabinósido de citosina durante siete días continuos y una antraciclina durante tres días), y 33 fueron tratados con el esquema TADOP (thioguanina, arabinósido de citosina, doxorrubicina, vincristina y prednisona). Los resultados fueron los siguientes: el número de ciclos para lograr la RC entre el esquema 7 + 3 y el TADOP mostró diferencias estadisticamente significativas: 1 versus 5 (p < 0.001). La remisión completa se logró en el 60 por ciento de los pacientes tratados con 7 + 3 y en el 48 por ciento de los pacientes con TADOP (p NS); la mediana de duración de la RC fue de 21 y 10 meses respectivamente (p < 0.05); la mielotoxicidad fatal se observó en el 30 por ciento y 42 por ciento respectivamente (p NS); la causa de muerte durante la inducción fue hemorragia en 53 por ciento y 57 por ciento para cada grupo respectivamente (p NS); la supervivencia total a un año fue de 50 por ciento y 54 por ciento (p NS), a los 36 meses de 22 por ciento y 15 por ciento (p NS) y la supervivencia libre de enfermedad a un año, 46 por ciento y 45 por ciento respectivamente (p NS). Se subclasificaron estos grupos en pacientes quienes recibieron tratamientos mielosupresores intensos (7 + 3) y fueron apoyados con transfusiones plaquetarias suficientes y obtenidas por citaféresis; los que recibieron 7 + 3 y se apoyaron con plaquetas obtenidas a partir de centrifugación y los que recibieron TADOP cuyo apoyo fue en todos los casos con plaquetas obtenidas por centrifugación; la supervivencia total a un año mostró diferencias significativas: 75 por ciento, 22 por ciento, y 54 por ciento, respectivamente (p < 0.01). La cantidad promedio de plaquetas transfundidas por pacientes fue de 24.4, 13.3 y 7.0 respectivamente (p < 0.01). Con estos datos podemos concluir que un esquema como el TADOP puede ser de utilidad cuando no se cuenta con un apoyo transfusional adecuado; sin embargo, la mejor opción terapéutica en pacientes con leucemia aguda mieloblástica es la administración de quimioterapia mielosupresora agresiva con apoyo transfusional óptimo por la técnica de citaféresis, por lo que consideramos que los pacientes con LAM deben tratarse preferentemente en sitios que cuentan con una infraestructura de apoyo transfusional adecuada

Acute non-lymphoblastic leukemia in children: prognostic factors and results of chemotherapy.

Twenty-nine children (age range 1-14, median 8 years) with acute non-lymphoblastic leukemia (ANLL) were induced in remission with daunorubicin and cytosine arabinoside. Twenty-three (79.3%) patients achieved complete remission (CR) and were administered two cycles of the same drugs as consolidation therapy; no maintenance treatment was given. Three (10.3%) patients died during induction; 3 (10.3%) patients were resistant to therapy. Multivariate analysis showed that female sex, TLC less than 50 X 10(9)/L, absence of in ection, albumin greater than 3.5 g/dl and high myeloperoxidase activity had a favourable influence on achievement of CR. TLC less than 50 X 10(9)/L and albumin greater than 3.5 g/dl also had a favourable prognostic value. Eight patients are alive between 13 and 32 months with overall survival at 2 years being 27.5%; four patients are free of disease with projected DFS at 2 years being 13.7%. The present data indicates the need for newer approaches to improve the long term survival in childhood ANLL.