Contaje absoluto de linfocitos como factor pronóstico en la leucemia aguda linfoblástica del niño / Absolute lymphocyte count as a prognostic factor in children with acute lymphoblastic leukemia

Introducción: Estudios recientes sugieren el contaje absoluto de linfocitos (CAL) como un nuevo indicador pronóstico en enfermedades malignas, de forma que aquellos pacientes que posean CAL superiores en determinados momentos del tratamiento, tendrán mayores posibilidades de supervivencia. En particular se ha visto la influencia de las células T y las células naturales asesinas en la inmunidad de pacientes con cáncer. Materiales y métodos: Se realizó un estudio retrospectivo en pacientes pediátricos con leucemia aguda linfoblástica tratados en el Instituto de Hematología e Inmunología entre los años1995 y 2008 (105 pacientes), con el objetivo de evaluar la influencia del conteo absoluto de linfocitos como factor pronóstico en la sobrevida libre de enfermedad (SLE) y la sobrevida global (SG) a los 5 años. Resultados: Evolucionaron desfavorablemente 24,8% y la mediana del CAL determinado los días 15 y 28 de tratamiento de estos pacientes fue de 1.000 células/ l. Los pacientes con CAL el día 15 (CAL-15) y 28 (CAL-28) <1.000 y ≥ 1.000/ l, mostraron una SLE de 51% vs 83% y 55%vs 82% (p = 0,02 y p = 0,04), respectivamente. Igualmente la SG para aquellos con CAL-15 yCAL-28 ≥1.000/ l fue 89% y 86% contra un 59% y 66% para valores <1.000 (p = 0,001 y p = 0,01),respectivamente. Al realizar el análisis multivariado junto a otros factores de riesgo como la edad, el estudio molecular, la respuesta al tratamiento y el contaje inicial de leucocitos, el CAL-15 mostró significación estadística tanto para la SLE (p = 0,006) como para la SG (p = 0,001). Conclusiones: El CAL fue un predictor significativo de supervivencia y recaída. Además tuvo un comportamiento independiente como factor pronóstico (AU)

Introduction: Recent studies have suggested that the absolute lymphocyte count (ALC) may bea prognostic indicator in malignant diseases, in that those patients who have higher ALC at certain times during treatment may have a better chance of survival. The influence of T cellsand natural killer cells in the immune system of the patient with cancer as a response to cancercells is particularly noted. Materials and Method: We prospectively assessed the prognostic value of absolute lymphocytic count (ALC) in 105 pediatric patients with acute lymphoblastic leukemia (ALL), treated in the Cuban Immunology and Hematology Institute from 1995 to 2008. ALC was studied at days 15 (ALC-15) and 28 (ALC-28) of treatment. Results: In our patients, 1000 cells/uL was the median ALC value for patients who relapsed ordied. Using 1000/uL we found that ALL patients with an ALC-15 <1000 cells/ l had a 5-year relapse free survival (RFS) of 51%. In contrast, an ALC-15 >1000 cells/uL showed an excellent prognosis, with a 5-year RFS of 83% (p=0.02). Similarly in our study, an ALC-28 <1000 cells/ lpredicted a 5-year overall survival (OS) of 66%, where as an ALC-28 >1000 cells/ l predicted excellent outcome, with a 5-year OS of 86% (p=0.01). Importantly, ALC is also a strong predictorin multivariate analysis with known prognostic factors. ALC is a simple, statistically powerful measurement for patients with de novo ALL. Conclusions: The results, when combined with previous studies, demonstrate that ALC is a powerful new prognostic factor for a range of malignancies (AU)

[Absolute lymphocyte count as a prognostic factor in children with acute lymphoblastic leukemia]. / Contaje absoluto de linfocitos como factor pronóstico en la leucemia aguda linfoblástica del niño.

INTRODUCTION: Recent studies have suggested that the absolute lymphocyte count (ALC) may be a prognostic indicator in malignant diseases, in that those patients who have higher ALC at certain times during treatment may have a better chance of survival. The influence of T cells and natural killer cells in the immune system of the patient with cancer as a response to cancer cells is particularly noted. MATERIALS AND METHOD: We prospectively assessed the prognostic value of absolute lymphocytic count (ALC) in 105 pediatric patients with acute lymphoblastic leukemia (ALL), treated in the Cuban Immunology and Hematology Institute from 1995 to 2008. ALC was studied at days 15 (ALC-15) and 28 (ALC-28) of treatment. RESULTS: In our patients, 1000 cells/uL was the median ALC value for patients who relapsed or died. Using 1000/uL we found that ALL patients with an ALC-15 <1000 cells/µl had a 5-year relapse free survival (RFS) of 51%. In contrast, an ALC-15 >1000 cells/uL showed an excellent prognosis, with a 5-year RFS of 83% (p=0.02). Similarly in our study, an ALC-28 <1000 cells/µl predicted a 5-year overall survival (OS) of 66%, whereas an ALC-28 >1000 cells/µl predicted excellent outcome, with a 5-year OS of 86% (p=0.01). Importantly, ALC is also a strong predictor in multivariate analysis with known prognostic factors. ALC is a simple, statistically powerful measurement for patients with de novo ALL. CONCLUSIONS: The results, when combined with previous studies, demonstrate that ALC is a powerful new prognostic factor for a range of malignancies.

Autotrasplante de células madre adultas en miembros inferiores con isquemia crítica / Adult stem cell autotransplantation in chronic critical limb ischemia

INTRODUCCIÓN. Recientemente se ha hecho evidente el potencial terapéutico de las células madre adultas en el tratamiento de arteriopatías periféricas, pues la implantación en los miembros isquémicos de células mononucleares procedentes de la médula ósea (CMN-MO) o de la sangre periférica (CMN-SP) puede mejorar la vascularization del tejido. MATERIAL Y MÉTODO. Se trataron 30 pacientes con isquemia critica de un miembro inferior, en los que no existía ninguna posibilidad de revascularización por métodos tradicionales. En 13 se implantaron CMN-MO autólogas en el miembro isquémico y en 17 se utilizaron CMN-SP. Los pacientes se monitorearon durante 24 semanas con el índice de presiones tobillo-brazo (ITB) en reposo, la distancia de marcha sin claudicación y la evaluación de la escala del dolor de reposo. RESULTADOS. Veintiún pacientes tenían indicación de amputación mayor del miembro afectado y en catorce (67%) de ellos se logró evitar. Tanto en los pacientes en que se emplearon CMN-MO como en los que recibieron CMN-SP hubo mejoría significativa del ITB en el miembro en que se hizo la implantación celular. El dolor de reposo mejoró significativamente en ambos grupos a las 4 semanas y a las 24 semanas había desaparecido. La distancia de marcha sin claudicación mejoró progresivamente en los dos grupos. En ningún caso se observaron efectos adversos secundarios al tratamiento. CONCLUSIONES. Los métodos de implantación de CMN-MO y de CMN-SP autólogas en pacientes con isquemia crítica de miembros inferiores resultaron procedimientos eficaces y sin complicaciones, lo que estimula a la continuación de los estudios clínicos en este campo (AU)

INTRODUCTION. Recently the therapeutic potential of adult stem cells in the treatment of peripheral arterial diseases has become increasingly evident, since implantation of bone marrow mononuclear cells (BM-MNC) or peripheral blood mononuclear cells (PB-MNC) into ischemic limbs can improve tissue vascularization. PATIENTS AND METHODS. Thirty patients with severe unilateral lower limb ischemia, with no option for standard revascularization therapies, were treated. Autologous BM-MNC were implanted into the ischemic limb in 13 cases and 17 received PBMNC. The patients were monitored during 24 weeks with resting ankle-brachial pressure index (ABI), pain-free walking distance and rest pain scale evaluation. RESULTS. Twenty one patients had been specifically advised to undergo major limb amputation that was avoided in 14 (67%). ABI significantly improved in the treated limb in both groups. Rest pain significantly improved in both groups at week 4 and at 24 weeks patients were completely pain-free. Pain free walking distance progressively improved in both groups. No related adverse effects were observed in any patient throughout the therapeutic procedure. CONCLUSIONS. The methods of autologous BM-MNC and PB-MNC implantation in patients with critical lower limb ischemia showed to be effective procedures without related complications. These results encourage to continue clinical studies in this field (AU)

Autologous bone-marrow mononuclear cell implantation in patients with severe lower limb ischaemia: a comparison of using blood cell separator and Ficoll density gradient centrifugation.

Different studies have provided evidence that implantation of bone-marrow mononuclear cells (BM-MNC) into ischaemic limbs can improve tissue vascularization. Based on these results we performed a pilot study in patients with critical lower limb ischaemia to assess efficacy and safety of implantation of autologous BM-MNC. The amount and efficacy of BM-MNC purified either by an automated method or by a manual procedure were compared. Twelve patients with severe unilateral lower limb ischaemia were entered into this study. They were randomly assigned to be injected with BM-MNC sorted on a blood cell separator or isolated by density gradient on Ficoll-Hypaque. BM-MNC were implanted into the ischaemic legs. Patients were monitored with resting ankle-brachial pressure index (ABI), arterial oxygen saturation (SaO(2)), pain-free walking time and rest pain scale evaluation. The automated and manual methods used for mononuclear cell separation gave results not significantly different. Monitored variables improved in both groups. Improvement of ischaemic condition persisted during 24 weeks follow-up. Limb salvage was achieved in five cases. Our results indicate that BM-MNC implantation into ischaemic limbs is a practical, safe and effective method that may significantly contribute to the management of patients with limb ischaemia. The Ficoll method is a simple and effective procedure for BM-MNC concentration that may be useful, mainly in hospitals without sophisticated facilities.

Thrombocytosis in patients with acute promyelocytic leukaemia during all-trans retinoic acid treatment.

In 26 acute promyelocytic leukaemia (APL) patients treated with all-trans retinoic acid (ATRA), 23% had platelet counts between 459 and 800 x 10(9)/I during treatment. These values, observed between days 28 and 45 of ATRA treatment, were transient and asymptomatic. We report two APL cases with platelet counts > 1000 x 10(9)/I during ATRA therapy who were treated with recombinant interferon alpha. In both cases ATRA doses were not modified, no complications secondary to thrombocytosis were seen, and they subsequently achieved complete remission. It is suggested that IL-6 may play an important role in the pathogenesis of the thrombocytosis induced by ATRA. To our knowledge, this is the first report of thrombocytosis occurring during ATRA treatment.

[Treatment of promyelocytic leukemia with retinoic acid: results in Cuba]. / Tratamiento de la leucemia promielocítica con ácido retinoico: resultados en Cuba.

PURPOSE: To assess the results attained with all-trans-retinoic acid (ATRA) in a group of Cuban patients with acute promyelocytic leukaemia (PML). PATIENTS AND METHODS: Twenty-one patients with PML were studied. Their cytogenetic study was performed with G-band techniques. ATRA was given orally as a single dosis of 50 mg/m2 a day, or divided in two doses. After attaining complete remission (CR), ATRA was maintained for 1-3 months in association with minimal doses of Ara-C or alpha-interferon. A rotation of three therapeutic regimes (TRAP, POMP and DOAP) was subsequently administered. RESULTS: Twelve of the patients were women and 9 men; 15 were adults and 6 were children, the median age being 19 years (range: 6-60 years). Only two patients had leucocytosis, all others presented with leucopenia. Platelet count below 30 x 10(10)/L was found in 67% of the cases, while some sort of bleeding was present in 81% of them. Laboratory evidence of disseminated intravascular coagulation was seen in 52% of the cases, and t (15; 17) appeared in 67% of the evaluable cytogenetic studies. CR was attained in 17 patients (81%) within a mean of 40 days. Headache was the commonest untoward effect of the treatment. Eight patients developed leucocytosis during treatment, white-cell count being over 20 x 10(9)/L in six of them. Fever without infectious signs was present in 5 patients, and in 3 of them the temperature recovered with steroid therapy. Two patients had retinoic acid syndrome prior to achieving CR. Four patients relapsed and 13 (76%) have maintained CR after 1 to 24 months. CONCLUSIONS: The incidence of CR in this series is within the limits reported in the literature. The secondary effects of the treatment are the same than those reported by others, and they were transient and well tolerated. The response to steroids of those patients with fever secondary to ATRA is noteworthy. The efficacy of ATRA, in general terms, in the induction of CR in PML seems confirmed by these results.

All-trans retinoic acid in acute promyelocytic leukemia: preliminary results in Cuba.

Seven patients with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (ATRA). Five (71.4%) achieved complete remission (CR). Most side effects were transient and well tolerated. Hyperleukocytosis was the major adverse effect. These observations confirm the efficacy of ATRA for inducing CR in APL.

Clinical features of hepatic sequestration in sickle cell anaemia.

Episodes of hepatic sequestration were seen in four patients with sickle cell anaemia (SCA). One case presented a severe and fatal sequestration crisis whereas the others showed mild episodes associated with less striking haematological and clinical changes. These clinical pictures are similar to those seen in the splenic sequestration crises of children with SCA. Different causes of liver enlargement in SCA suggest that the clinical spectrum representing intrahepatic trapping of blood could range from the acute sequestration crisis to chronic sequestration events which very probably should play any role in the pathogenesis of the hepatomegaly frequently found in these patients.

Sarcoidosis associated with autoimmune haemolytic anaemia and paroxysmal nocturnal haemoglobinuria red cell abnormality.

A 29-year-old male with sarcoidosis autoimmune haemolytic anaemia and paroxysmal nocturnal haemoglobinuria is described. Throughout his illness the chest films showed fibrosis in the right hilar region and he had had several pneumonias in the right lung. He had had massive splenomegaly and a splenectomy was performed. He was treated with prednisone and cyclophosphamide. Because his blood group was initially confused, several incompatible blood transfusions were given. Two types of antibody were detected: an autoantibody with "s" specificity and an alloantibody with Rh "D" specificity. Other interesting features in this case revealed at autopsy were a viral pneumonia and Toxoplasma gondii infection of the brain. As far as we know, this is the first reported patient with this unusual association.