Experience with treatment of pulmonary alveolar proteinosis from a tertiary care centre in north India.

Background. Pulmonary alveolar proteinosis (PAP) is a disorder characterised by accumulation of lipids and proteins in the alveoli, with the resultant symptoms ranging from indolent subclinical disease to progressive respiratory failure. Methods. We retrospectively studied five patients with PAP managed at our center between January 2007 and April 2010, with whole lung lavage (WLL) and/or subcutaneous granulocyte macrophage-colony stimulating factor (GM-CSF) therapy. Patients undergoing WLL under general anaesthesia were supplemented with three months of GM-CSF therapy. Pre- and post-lavage symptom assessment was performed with a 10-point, symptom-based visual analogue scale. Results. Their mean age was 37.6±7.0 years; there were four males. Diagnosis of PAP [idiopathic (n=3); secondary to Nocardia (n=1)] was established by surgical lung biopsy in four patients who presented with respiratory failure. Three patients with idiopathic PAP (n=3) were treated with a combination of GM-CSF and WLL; one patient with secondary PAP was treated with antibiotics alone. In another patient transbronchial lung biopsy was used to diagnose PAP and GM-CSF alone was administered. All patients were followed up for a median period of two years (range 0.5-3 years). Significant improvement was achieved in all the patients with therapeutic WLL and/or GM-CSF. Conclusions. Whole lung lavage appeared to be an effective and safe therapy in patients with PAP. Efficacy of simultaneous administration of GM-CSF and WLL in the treatment of PAP merits further study.

Hematopoietic growth factors in drug-induced agranulocytosis.

Drug-induced agranulocytosis (DIA) is a potentially fatal disorder. Hematopoietic growth factors have been used in the treatment of DIA. We report nine cases of DIA treated with granulocyte macrophage - colony stimulating factor (GM-CSF) in a dose of 300 microg/day. All the patients had evidence of systemic infection. Mean time to reach an absolute neutrophil count of 0.5 x 10(9)/L was three days. One patient succumbed to the disease. The cause of death was multiorgan failure. No adverse events were observed with GM-CSF. We conclude that hematopoietic growth factors are useful in shortening the period of neutropenia and reducing morbidity and mortality in these patients.

Reversal of paclitaxel induced neutropenia by Withania somnifera in mice.

The effect of aqueous extract of Withania somnifera (L. Solanaceae) was studied against paclitaxel induced neutropenia in mice. After paclitaxel 1 mg/kg, i.v. administration significant fall in total WBC and absolute neutrophil count was observed on day 3 and day 5. W. Somnifera (200 mg/kg, p.o.) per se produced significant increase in neutrophil counts. W. somnifera (200 mg/kg, p.o.) when administered for 4 days before paclitaxel treatment and continued for 12 days caused significant reversal of neutropenia of paclitaxel. The findings of the study suggest the potential of W. somnifera as an adjuvant during cancer chemotherapy for the prevention of bone marrow depression associated with anticancer drugs.

The effect of GM-CSF (granulocyte macrophage colony stimulating factor) on doxorubicin induced tissue necrosis and wound healing.

PURPOSE: The effect of GM-CSF (granulocyte macrophage-colony stimulating factor) on tissue necrosis and ulceration induced with doxorubicin extravasation was studied. MATERIALS AND METHODS: Adult Wistar-Albino rats (n=36) were used in the study. Doxorubicin (0.4mg/300 g) was applied subcutaneously to abdominal wall. In group I (n=18), half hours after doxorubicin injection, GM-CSF 6 microg/300 mg was applied subcutaneously to the same localization. In group II (n = 18) same amount of physiologic saline (0.5 ml) were given subcutaneously to the injection site (as vehicle control groups). Group II and I were examined for induration or ulceration on 7th and 21st day. After evaluating the lesions, the injection sites were excised. Hydroxyproline (5-HP) values of dry tissue samples were calculated and histopathologic examination was done. RESULTS: At day seven there were four and eight ulceration in groups I and II, while there were four and 14 ulceration in the second evaluation at day 21st (p<0.05). 5-HP values of the groups were as follows. 97.43+/-20.39 in group land 91.34+/-22.26 in group II. Although there was an increase in epithelization, eosinophil and lymphocyte infiltration and mast cell number in group I in histopathologic examinations only the increase in angiogenesis in group I was found to be statistically significant (p<0.05). CONCLUSION: It can be concluded that GM-CSF may have beneficial effect in the treatment of doxorubicin induced tissue necrosis.

Granulocyte macrophage-colony stimulating factor (GM-CSF) in neonatal neutropenia.

Neutropenia in neonates is often associated with sepsis, prematurity and maternal hypertension with increased risk of mortality. We describe two neonates with neutropenia treated with granulocyte macrophage colony stimulating factor. The total and absolute neutrophil counts showed a marked response and led to a favourable outcome. Human granulocyte macrophage colony stimulating factor may be used as an adjuvant therapy for neonatal neutropenia of different aetiologies.

Increased levels of multiple forms of dihydrofolate reductase in peripheral blood leucocytes of cancer patients receiving haematopoietic colony-stimulating factors: interim analysis

The precise mechanism whereby granulocytes proliferate when haematopoietic colony stimulating factors (CSFs) are used in neutropenic cancer patients is poorly understood. The purpose of this study was to investigate whether these cytokines bring about leucocyte proliferation by increasing the levels of multiple forms of dihydrofolate reductase (DHFR). Blood samples were collected from 36 cancer patients (25 males and 11 females) with chemotherapy-induced neutropenia. One sample of blood from each patient was obtained before therapy either with CSF, such as granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) or with placebo, and another one at the time of resolution of neutropenia. Peripheral blood leucocytes in these blood samples were counted, separated and lysed. From lysates, cytoplasmic samples were prepared and analyzed for active DHFR by a methotrexate-binding assay and for total immunoreactive DHFR by an enzyme linked immunosorbent assay. The increase in total leucocyte count (TLC) was most prominent (P < 0.005) in the CSF group and less so (P < 0.05) in the placebo group. The mean +/- SD concentration values of active DHFR before and after stimulation with GM-CSF found were to be 0.34 +/- 0.4 ng/mg protein and 0.99 +/- 0.82 ng/mg protein, respectively, and in the group treated with G-CSF, 0.24 +/- 0.32 ng/mg protein and 1.18 +/- 2.4 ng/mg protein, respectively. This increase in active DHFR after stimulation with CSF was statistically significant (P <0.05). Similarly, concentration values of immunoreactive but nonfunctional form of DHFR (IRE) were 110 +/- 97 ng/mg protein and 605 +/- 475 ng/mg protein before and after stimulation with GM-CSF, and 115 +/- 165 ng/mg protein and 1,054 +/- 1,095 ng/ mg protein before and after stimulation with G-CSF. This increase in concentration of IRE after stimulation with GM-CSF or G-CSF was statistically significant (P < 0.005). In the control group, there was an increase in the concentration of both active DHFR and IRE after treatment with placebo. However, this was not statistically significant. Resolution of neutropenia was quicker in the groups treated with CSF compared to the control group. Results of this study indicate that colony stimulating factors (G-CSF and GM-CSF) induce white cell proliferation by increasing the levels of multiple forms of DHFR.

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.

Algunas observaciones sobre un caso clínico de granulocitosis por metimazol / Some considerations about a clinical case of agranulocytosis with methimazole

Se informa el caso de una mujer de 39 años con bocio tóxico difuso que padeció agranulocitosis secundaria al tratamiento con metimazol. Durante el curso clínico de la enfermedad, la paciente desarrolló síndrome de insuficiencia respiratoria progresiva del adulto, padecimiento clínico que hasta hace poco no se reconocía en pacientes con agranulocitosis. El tratamiento incluyó apoyo intensivo de las fallas orgánicas en la unidad de cuidados intensivos (UCI), así como la administración intravenosa de factor estimulante de colonias granulocito-macrófago recombinante humano (rh GM-CSF), sin obtener respuesta en la producción de granulocitos después de siete días de tratamiento. Se observó una disminución de 12 mmHg promedio de la tensión arterial sistémica media durante la administración de este factor. La paciente murió por falla orgánica multisistémica siete días después de su ingreso a la UCI

Recombinant human granulocyte-macrophage colony stimulating factor as treatment for chronic leg ulcers

Objetivo. Evaluar la seguridad y efectividad de una sola aplicación subcutánea perilesional de 300 µg de factor estimulante de colonias de granulocito-macrófago (FEC-GM) en el tratamiento de úlceras crónicas de miembros pélvicos. Diseñó. Fue un estudio prospectivo y descriptivo realizado en el Centro Médico Nacional 20 de Noviembre, ISSSTE. Pacientes. 10 pacientes con úlceras crónicas de miembros pélvicos. Evaluación. Se realizaron mediciones secuenciales del diámetro de la úlcera así como de la presencia e intensidad de los efectos colaterales. Resultados. Tras cuatro semanas de observación, 8 de las 10 úlceras habían cerrado; las otras dos tuvieron una disminución promedio de su diámetro de 21 por ciento. El único efecto colateral encontrado fue en una mujer de 58 años la cual presentó dolor perilesional moderado dos días después de la administración del FEC-GM, el cual fue tratado exitosamente con paracetamol. Conclusión. Creemos que la aplicación perilesional de 300 µg de FEC-GM es un procedimiento efectivo y seguro para el tratamiento de las úlceras crónicas de miembros pélvicos

Prevención de mielotoxicidad en un caso de transplante medular con factor estimulante de colonias granulacito-macrófago asociado a ganciclovir / Use of GM-CSF as prophylaxis of ganciclovir-induced severe bone marrow suppression

Se informa la primera experiencia mexicana con el uso de factor estimulante de colonia granulocito-macrófago (GM-CSF) com profilaxis de la neutropenia secundaria a ganciclovir, en la prevención de la enfermedad por citomegalovirus (CMV) en un paciente CMV sero-positivo con leucemia mieloide aguda en primera remisión, trasplantando con donador HLA idéntico y CMV sero-positivo. La toma de injerto ocurrió el día 14. Se inició ganciclovir 5 mg/kg/3 veces por semana) en el día 35 acompañandose de toxicidad medular secundaria 28 días después con neutropenia grave que remitió de manera espontánea posterior a la suspensión del mismo. A fin de concluir el esquema de profilaxis, se inició GM-CSF a dosis de 300 mg/kg/día concomitante al ganciclovir a dosis de 5 mg/kg/día con lo cual fue posible conluir tratamiento sin que se reindujera toxicidad medular. No hubo evidencia de enfermedad de injerto contra huésped ni de infección por CMV. La evolución del paciente fue satisfactoria durante un año, posterior al cual, presentó recaída de su enfermedad de base mueriendo por complicaciones secundarias a leucemia

GM-CSF and low-dose araC treatment of AML in prolonged hypoplasia with residual leukemic cells after induction chemotherapy

We describe a case with acute myelogenous leukemia (AML; M2) who developed prolonged marrow hypoplasia with residual leukemic blasts and recurrent infections after induction chemotherapy. He was treated successfully with a sequential treatment of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and low-dose cytosine arabinoside (LD AraC). To the best of our knowledge this is the first reported case of a successful treatment of a patient with AML, who showed prolonged markedly hypocellular bone marrow with significant residual leukemic cells after induction chemotherapy, with a sequential treatment of GM-CSF and LD AraC.

Epidemiologia e prevençäo da infecçäo no hospedeiro granulocitopênico / Epidemiology and prevention of infection diseases in lemopenic patients

A susceptibilidade à infecçäo aumenta dramaticamente quando a contagem periférica de neutrófilos cai abaixo de 500cels/mm3, e particularmente quando abaixo de 100cls/mm3. A rapidez da queda dos granulócitos e a duraçäo da aplasia estäo mais associados com os quadros infecciosos. Culturas de vigilância têm mostrado um valor limitado em predizer uma infecçäo invasiva em pacientes neutropênicos ou com câncer. O isolamento protetor simples em pacientes com granulocitopenia parece näo beneficiar a profilaxia das doenças infecciosas. O uso de descontaminaçäo digestiva seletiva, reduziu infecçöes do trato respiratório e septcemias bacterianas em crianças. O objetivo deste procedimento é eliminar microorganismos patogênicos potenciais, como Enterobacteriaceae, P. aeruginosa e Staphilococci. Os estudos mais recentes têm discutido o uso de Fator estimulador de colonias (CSF) associado a interferon-gama para prevençäo de infecçöes nesses pacientes

Factores de crecimiento hematopoyético: su utilidad en oncología clínica (primera parte) / Hematopoyetic growth factors: its utility in clinical oncology

Los factores de crecimiento hematopoyético (factor estímulante de colonias de granulocitos y macrófagos: GM-CSF; factor estímulante de granulocitos: G-CSF; factor estímnulante de colonias de macrófagos: M-CSF; interleukina 3: IL3) tienen acciones pleiotrópicas sobre la proliferación y diferenciación de las clulas progenitoras hematopoyéticas, y recientemente han ingresado al uso clínico, puesto que ya han demostrado su amplia eficacia y utilidad en diversas situaciones. Pueden mejorar la neutropenia de los síndromes mielodisplásicos y de anemia aplásica. También pueden acelerar la recuperación luego del trasplante de médula ósea y así reducir la morbilidad concomitante a este procedimiento. También pueden incrementar el reclutamiento y cosecha de progenitores de sangre periférica y de ese modo afectar significativamente la posiblilidad de suministar quimioterapía intensiva, con o sin trasplante de médula ósea. Su uso pot6encial más importante se centra en la posibilidad de paliar la neutropenia que sigue a la terapía mielosupresora en pacientes con SIDA y con cáncer que reciben quimioterapía. Los factores de crecimiento hematopoyético han demostrado eficacia en disminución de la duración de la neutropenia, disminución de las infecciones concomitantes y un aumento de la habilidad para suministrar dosis plenas de quimioterapía mielosupresora