Dose Intensive Rituximab and High-Dose Methylprednisolone in Elderly or Unfit Patients with Relapsed Chronic Lymphocytic Leukemia.

Background and Objectives: BTK and BCL2 inhibitors have changed the treatment paradigms of high-risk and elderly patients with chronic lymphocytic leukemia (CLL), but their long-term efficacy and toxicity are still unknown and the costs are considerable. Our previous data showed that Rituximab (Rtx) and high-dose methylprednisolone (HDMP) can be an effective and safe treatment option for relapsed high-risk CLL patients. Materials and Methods: We explored the efficacy and safety of a higher Rtx dose in combination with a shorter (3-day) schedule of HDMP in relapsed elderly or unfit CLL patients. Results: Twenty-five patients were included in the phase-two, single-arm trial. The median progression free survival (PFS) was 11 months (range 10-12). Median OS was 68 (range 47-89) months. Adverse events (AE) were mainly grade I-II° (77%) and no deaths occurred during the treatment period. Conclusions: 3-day HDMP and Rtx was associated with clinically meaningful improvement in most patients. The median PFS in 3-day and 5-day HDMP studies was similar and the toxicity of the 3-day HDMP schedule proved to be lower. The HDMP and Rtx combination can still be applied in some relapsed high-risk and elderly or unfit CLL patients if new targeted therapies are contraindicated or unavailable. (ClinicalTrials.gov identifier: NCT01576588).

Treatment of pure red cell aplasia after major ABO-incompatible bone marrow transplantation resistant to erythropoietin. Bone Marrow Transplantation Team.

A case of pure red cell aplasia after major ABO-incompatible bone marrow transplantation with long duration of up to 482 days is presented. The patient exhibited resistance to treatment using intravenous gamma globulin, prednisolone and 8 week administration of erythropoietin. The patient finally responded to treatment using erythropoietin and methylprednisolone simultaneously. Because of its safety and efficacy, it might be worthwhile to try erythropoietin with methylprednisolone, if necessary, for pure red cell aplasia complicating major ABO-incompatible bone marrow transplantation.

Cyclosporine combined with methylprednisolone or methotrexate in prophylaxis of moderate to severe acute graft-versus-host disease.

To evaluate the efficacy of cyclosporine (CYA) regimens in preventing moderate to severe acute graft-versus-host disease (GVHD), 25 patients received immunosuppressive therapy consisting of either CYA and methylprednisolone or CYA and methotrexate (MTX) and the incidence and severity of acute GVHD was compared. These patients had leukemia or myelodysplastic syndrome (MDS) and received bone marrow transplants (BMT) from genotypically HLA-identical siblings. The incidence of grade I-IV acute GVHD in patients on the CYA/methylprednisolone regimen was 64% (7 of 11) compared with 50% (7 of 14) in those on the CYA/MTX regimen. Five of 11 patients with the CYA/methylprednisolone regimen developed moderate to severe acute GVHD (grade II-IV), fatal in 3 cases. No patient on the CYA/MTX regimen developed moderate to severe acute GVHD. Engraftment was faster in the CYA/methylprednisolone group than in the CYA/MTX group. The incidence of toxicity observed soon after BMT was comparable between groups. The CYA/MTX regimen may be superior to the CYA/methylprednisolone regimen for preventing moderate to severe acute GVHD.

Purity evaluation of 6 alpha-methylprednisolone acetate by HPLC.

A high-performance liquid chromatographic method is described for the analysis and identification of related impurities in pharmaceutical-grade 6 alpha-methylprednisolone acetate (MPA). Eight MPA impurities derived from synthesis and/or degradation processes were identified. The method is compared to other analytical procedures recently proposed for the European Pharmacopoeia.

Corticosteroids and bioavailability.

This presentation has attempted to provide a brief view of the importance of bioavailability and bioequivalence to those physicians who use corticosteroids. In particular it emphasizes that in vitro tests may not be reliable for predicting variability between formulations and, more importantly, cannot take the place of a bioavailability study. The implication would seen clear: namely, that a manufacturer who wishes to market a formulation similar to that already available and found to be acceptable clinically cannot rely on merely matching the standard formulation with in vitro tests but should substantiate that his formulation is, indeed, bioequivalent to the standard. In addition, data have been presented that clearly suggest the importance of bioavailability methodology as a new and useful pharmacological tool. In conclusion, as far as the bioavailability of corticosteroids in the marketplace is concerned, an old adage may be paraphrased: "If you don't know your bioavailability, know your manufacturer."

Bloqueio analgésico peridural lombar para tratamento de lombociatalgia discogênica: estudo clínico comparativo entre metilprednisolona e metilprednisolona associada à levobupivacaína / Lumbar epidural anesthesia in the treatment of discal lombosciatalgia: a comparative clinical study between methylprednisolone and methylprednisolone with levobupivacaine

JUSTIFICATIVA E OBJETIVOS: A técnica peridural lombar tem sido utilizada no tratamento da lombociatalgia desde 1953. Na maioria das vezes, emprega-se metilprednisolona adicionada a um anestésico local e não se sabe se seu uso isolado tem a mesma eficácia no alívio dos sintomas. O objetivo deste estudo foi comparar a eficácia de duas soluções diferentes - metilprednisolona com soro fisiológico e metilprednisolona com levobupivacaína -, injetadas no espaço peridural para tratar lombociatalgia devido à hérnia discal lombar. MÉTODO: Participaram deste estudo 60 indivíduos, ASA I e II, no período de um ano, submetidos à técnica analgésica peridural lombar interlaminar para tratamento da lombociatalgia sem controle radioscópico, de ambos os sexos, com idade entre 18 e 65 anos, divididos em dois grupos: G-M (metilprednisolona + solução fisiológica a 0,9 por cento) e G-M + L (metilprednisolona + levobupivacaína + solução fisiológica a 0,9 por cento), ambos em um volume de 10 mL. O diagnóstico se baseou na história, no exame físico e em exame por imagem (ressonância magnética nuclear). O trabalho foi conduzido de forma duplo-encoberta, com seleção aleatória dos participantes. Foi aplicada a Escala Analógica Visual (EAV) em um total de dois bloqueios, um a cada 15 dias. RESULTADOS: Houve redução mais significativa da intensidade da dor para o grupo metilprednisolona + levobupivacaína, porém sem significância estatística. CONCLUSÕES: A solução do G-M + L demonstrou eficácia analgésica superior à solução do G-M para o tratamento da lombociatalgia discogênica no que diz respeito ao menor tempo para início da analgesia, mas não de forma significativa, no momento da alta, sendo as duas soluções eficazes no tratamento da lombociatalgia radicular discogênica.

BACKGROUND AND OBJECTIVES: Lumbar epidural technique has been used in the treatment of lombosciatalgia since 1953. In most cases, methylprednisolone is used along with a local anesthetic, and it is not known whether the isolated use of methylprednisolone is equally effective in relieving symptoms. The objective of this study was to compare the efficacy of two different solutions - methylprednisolone with saline and methylprednisolone with levobupivacaine injected in the epidural space to heal lombosciatalgia secondary to lumbar herniated disk. METHODS: Sixty individuals ASA I and II, of both genders, ages 18 to 65 years participated in this randomized, double-blind study over a period of one year. They underwent interlaminar lumbar epidural analgesia without radioscopic control to heal a lombosciatalgia and they were divided into two groups: G-M (methylprednisolone + saline) and G-M + L (methylprednisolone + levobupivacaine + saline) both at a volume of 10 mL. Diagnosis was based on history, physical exam, and imaging exam (MRI). The Visual Analogue Scale (VAS) was applied in a total of two blockades, 15 days apart. RESULTS: A reduction in pain severity was observed in the methylprednisolone-levobupivacaine group, but without statistical significance. CONCLUSIONS: The analgesic efficacy of the G-M + L solution was superior to that of the G-M solution in the treatment of discal lombosciatalgia regarding the shorter time to onset of analgesia, but this was not significant at the time of discharge, and both solutions were effective in the treatment of discal lombosciatalgia.

JUSTIFICATIVA Y OBJETIVOS: La técnica epidural lumbar ha sido utilizada en el tratamiento de la lumbociatalgia desde 1953. En la mayoría de los casos, se usa la metilprednisolona añadida a un anestésico local, y no se conoce si su uso aislado tiene la misma eficacia en el alivio de los síntomas. El objetivo de este estudio fue comparar la eficacia de dos soluciones diferentes: metilprednisolona con suero fisiológico y metilprednisolona con levobupivacaína, inyectadas en el espacio epidural, para tratar la lumbociatalgia debido a la hernia de disco lumbar. MÉTODO: Participaron en este estudio 60 individuos, ASA I y II, en el período de un año, sometidos a la técnica analgésica epidural lumbar interlaminar para el tratamiento de la lumbociatalgia sin control radioscópico, de ambos sexos, con una edad entre los 18 y los 65 años y que se dividieron en dos grupos: G-M (metilprednisolona + solución fisiológica al 0,9 por ciento) y G-M + L (metilprednisolona + levobupivacaína + solución fisiológica al 0,9 por ciento), ambos en un volumen de 10 mL. El diagnóstico estuvo basado en el historial, en el examen físico y en el examen por imagen (resonancia magnética nuclear). El trabajo fue realizado a doble ciego, con la selección aleatoria de los participantes. Se aplicó la Escala Analógica Visual (EAV), en un total de dos bloqueos, uno a cada 15 días. RESULTADOS: El resultado fue una reducción más significativa de la intensidad del dolor para el grupo metilprednisolona + levobupivacaína, pero sin significancia estadística. CONCLUSIONES: La solución del G-M + L demostró una eficacia analgésica superior a la solución del G-M para el tratamiento de la lumbociatalgia discogénica, en lo que se refiere al menor tiempo para el inicio de la analgesia, pero no de forma significativa en el momento del alta, siendo las dos soluciones eficaces en el tratamiento de la lumbociatalgia radicular discogénica.

A controlled trial of pulse cyclophosphamide versus pulse methylprednisolone in severe lupus nephritis.

We carried out a prospective randomized trial comparing pulse cyclophosphamide and pulse methylprednisolone in 29 patients with severe lupus nephritis in activity. Patients were assigned to one of two regimens: monthly pulse cyclophosphamide (0.5-1.0 g/m2 body surface area) for 4 months, followed by bimonthly doses for 4 months and quarterly doses for 6 months (14 patients) or pulse methylprednisolone (10-20 mg/kg weight) initially for 3 consecutive days and thereafter in the same intervals as the alternative regimen (15 patients). The mean follow-up was 15 months. Two patients in the cyclophosphamide group and three in the methylprednisolone group died. Renal failure (doubling of serum creatinine) developed in four patients in the cyclophosphamide group compared with five patients in the methylprednisolone group. Cumulative probability of not doubling serum creatinine was similar for cyclophosphamide and methylprednisolone groups (0.66 vs 0.69, respectively, P > 0.20, after 18 months). Cumulative probability of survival without renal failure was also not significantly different (0.61 and 0.63, respectively, P > 0.20, after 18 months). These results suggest that pulse cyclophosphamide is as effective as pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis.

Intravenous methylprednisolone pulse therapy in ankylosing spondylitis.

The aim of this double-blind study was to compare the effect of high-dose (1000 mg) and low-dose (375 mg) methylprednisolone pulse therapy administered intravenously once daily for three consecutive days, in active ankylosing spondylitis. Seventeen patients with active ankylosing spondylitis were randomly allocated to high-dose (8 patients) or low-dose (9 patients) regimen. Although there was no placebo group in this study, it is our impression that in patients with active ankylosing spondylitis, both high-dose (1000 mg) and low-dose (375 mg) methylprednisolone pulse therapy given on three consecutive days, is effective as regards pain relief and improvement in spinal mobility. There were no statistically significant differences between the two groups, though there was a trend towards the high dose yielding a greater and longer lasting improvement. No serious adverse reactions were observed.