Combination Of High-dose Methylprednisolone Research Articles

Successful treatment of HIV-associated progressive multifocal leukoencephalopathy (PML) with mirtazapine, mefloquine, and IVIG combination therapy: a case report.

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system caused by reactivation of the polyomavirus JC (JCV). Human immunodeficiency virus (HIV) infection is one of the leading causes of PML which has high morbidity and mortality due to the lack of a proven standard treatment. We found clinical and radiological improvement with the combination of high-dose methylprednisolone, mirtazapine, mefloquine, and IVIG in our patient who presented with neurological symptoms and had diagnosed concurrent acquired immunodeficiency syndrome (AIDS) and PML. To our knowledge, our case is the first HIV-associated PML which responded to this combination therapy.

Efficacy of high-dose methylprednisolone and cyclophosphamide in childhood-onset systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease. Untreated SLE often become progressive and lead to increased risk of mortality. Corticosteroid and cyclophosphamide remain the treatment of choice for severe SLE. Disease activity assessed with SLE Daily Activity Index (SLEDAI).
 Objective To compare the disease activity of childhood-onset severe SLE at the time of diagnosis, after completion of high dose methylprednisolone, and after three month of cyclophosphamide by using SLEDAI.
 Methods This study was conducted in the Division of Pediatric Allergy and Immunology, Department of Child Health, Udayana University/Sanglah Hospital, Denpasar, Bali. Subjects were SLE patient aged 0-18 years who had severe clinical manifestations. Subject received therapy combination of high dose methylprednisolone and cyclophosphamide every 2 weeks for six doses. SLEDAI score was assessed at the time of diagnosis, after completion of high dose methylprednisolone, and after three month of cyclophosphamide.
 Results During the study period, 51 children were diagnosed as SLE. Twenty-one subjects were included for analysis. Median SLEDAI score at the time of diagnosis was 23 (range 13-39). SLEDAI score after three months of cyclophosphamide was decreased to 2 (range 0-14). Post hoc analysis with Wilcoxon signed-rank test showed the improvement of SLEDAI score at the time of diagnosis and after three months of cyclophosphamide was statistically significant (Z=-4.016, P<0.0001).
 Conclusion SLEDAI score reduced after completion of high-dose methylprednisolone and three month of cyclophosphamide therapy.

Efficacy of high-dose methylprednisolone and cyclophosphamide in childhood-onset systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease. Untreated SLE often become progressive and lead to increased risk of mortality. Corticosteroid and cyclophosphamide remain the treatment of choice for severe SLE. Disease activity assessed with SLE Daily Activity Index (SLEDAI).
 Objective To compare the disease activity of childhood-onset severe SLE at the time of diagnosis, after completion of high dose methylprednisolone, and after three month of cyclophosphamide by using SLEDAI.
 Methods This study was conducted in the Division of Pediatric Allergy and Immunology, Department of Child Health, Udayana University/Sanglah Hospital, Denpasar, Bali. Subjects were SLE patient aged 0-18 years who had severe clinical manifestations. Subject received therapy combination of high dose methylprednisolone and cyclophosphamide every 2 weeks for six doses. SLEDAI score was assessed at the time of diagnosis, after completion of high dose methylprednisolone, and after three month of cyclophosphamide.
 Results During the study period, 51 children were diagnosed as SLE. Twenty-one subjects were included for analysis. Median SLEDAI score at the time of diagnosis was 23 (range 13-39). SLEDAI score after three months of cyclophosphamide was decreased to 2 (range 0-14). Post hoc analysis with Wilcoxon signed-rank test showed the improvement of SLEDAI score at the time of diagnosis and after three months of cyclophosphamide was statistically significant (Z=-4.016, P<0.0001).
 Conclusion SLEDAI score reduced after completion of high-dose methylprednisolone and three month of cyclophosphamide therapy.

Long-Term Follow up of Front-Line Therapy with Ofatumumab, High Dose Methylprednisolone and Lenalidomide (HiLO trial) for Treatment-Naïve Chronic Lymphocytic Leukemia

Background: New targeted therapies continue to show improved efficacy in various stages of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), sparing patients from chemoimmunotherapy. However, cure remains elusive. Here, we present a front-line alternative based on a combination of high-dose methylprednisolone (HDMP) and ofatumumab, followed by consolidative therapy with lenalidomide plus ofatumumab.Methods: This is a phase II, single-center study in patients with treatment-naive (TN) CLL/SLL. During the first treatment phase (cycles 1-3) patients received HDMP 1000 mg/m2 IV and ofatumumab 2000 mg (300 mg given week 1 then 2000 mg for a total of 12 doses) IV infusions weekly x 4 doses in cycle 1 of a 28 day cycle, then every 2 weeks for cycles 2 and 3. During the second treatment phase (cycles 4-12), patients received renally adjusted lenalidomide 5-10 mg daily and ofatumumab 2000mg IV once every 8 weeks. Growth factor support was permitted at the discretion of treating physician. Prophylactic medications included allopurinol for tumor lysis syndrome (TLS) 3 days before C1D1 through C1; and trimethoprim/sulfamethoxazole and fluconazole through cycle 4, and acyclovir through C12. Patients received aspirin 81 mg/day as thrombosis prophylaxis while on lenalidomide. Patients were assessed for response by iwCLL 2008 criteria (including imaging assessment) after completion of cycles 3 and 12. The study allowed continuation of lenalidomide if patients achieved complete (CR), partial (PR) response or stable disease (SD). Primary endpoints were efficacy, adverse events (AEs) profile, and time-to-treatment failure (TTF).Results: Between January 2012 and September 2015, the study enrolled a total of 45 patients. Median follow-up was 50.4 (5.6-72.8) months. The median age was 62.6 (48.2-86.1) years. Chromosomal analysis by FISH demonstrated Del17p in 8 (17.8%), Del11q (+/- others, except Del17p) in 10 (22.2%), Trisomy 12 (+/- others, except Del17p and Del11q) in 8 (17.8%), Del13q in 10 (22.2%), no mutations in 9 (20%) patients. The IGHV status was unmutated in 34 (75.6%) cases. Indications to start treatment were: symptomatic lymphadenopathy, symptomatic splenomegaly, anemia, and thrombocytopenia in 5 (11.1%), 10 (22.2%), 12 (26.7%), and 18 (40%), respectively. The median duration of treatment was 35.6 (2.7-66.9) months. Reasons for treatment discontinuation were: progressive disease (PD) in 9 (20%), AEs in 15 (33.3%), transplantation in 3 (6.7%), consent withdrawal in 1 (2.2%), and secondary malignancies in 2 (4.4%) cases. The overall response rates (PR+CR) at 3, 12, 24, 36, and 48 months were 75.6%, 77.8%, 66.7%, 44.4%, and 37.8%, respectively. The CR rates at 3, 12, 24, 36, and 48 months were 2.2%, 11.1%, 20%, 17.8%, and 13.3% respectively. Fifteen patients remain in PR/CR and on treatment at the time of this analysis. The intention-to-treat median TTF was 45.2 (2.9-69.7) months, and was not different among high risk groups such as Del17p, Del11q and/or unmutated IgHV. In patients who discontinued for reasons other than PD the median duration of response without treatment was 30.7 (9.8-69.7) months. Three (6.7%) patients underwent allogeneic hematopoietic cell transplantation after a median of 3 (3 - 4) treatment cycles.Treatment was well tolerated with grade 3/4 infusion reaction in 1 (2.2%) patient. Grade 3/4 treatment-related hematological AEs were neutropenia, thrombocytopenia, and anemia in 33 (73.3%), 5 (11.1%), and 1 (2.2%), respectively. Grade 3/4 infections occurred in 6 (13.3%) patients. No grade 3/4 tumor flares were observed, and there were no cases of TLS or thrombosis.Conclusion: The combination of ofatumumab, HDMP and lenalidomide is effective and well tolerated in treatment-naive CLL/SLL, even when poor prognostic features are present. DisclosuresKomrokji:Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau. Locke:Novartis Pharmaceuticals: Other: Scientific Advisor; Cellular BioMedicine Group Inc.: Consultancy; Kite Pharma: Other: Scientific Advisor. Kharfan-Dabaja:Seattle Genetics: Speakers Bureau; Incyte Corp: Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau. Sokol:Spectrum Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Mallinckrodt Pharmaceuticals: Consultancy.

Combination of High-Dose Methylprednisolone and Defibrotide for Veno-Occlusive Disease in Pediatric Hematopoietic Stem Cell Transplant Recipients

Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplant (HSCT), with high mortality in severe cases and until recently very limited therapeutic options consisting largely of supportive care. Defibrotide was recently approved in the United States for the treatment of severe VOD in patients with renal or pulmonary dysfunction after HSCT. Our group previously published on the use of high-dose methylprednisolone (500 mg/m2 per dose every 12 hours for 6 doses) in patients with VOD, showing good success. A small subset of these individuals were also treated with defibrotide, but additional studies using the combination of high-dose methylprednisolone and defibrotide for the treatment of VOD are lacking. We present a single-institution retrospective chart review of 15 HSCT patients with VOD treated with the combination of high-dose methylprednisolone and defibrotide. VOD developed at a median of 17 days post-HSCT, and combination therapy was initiated within 1 day of VOD diagnosis. Twelve of 15 patients (80%) had multiorgan failure. Our single-center experience using both high-dose methylprednisolone and defibrotide showed a day +100 survival rate of 73% and an overall VOD complete resolution rate of 66.7%, higher than the rates reported in the recent literature using defibrotide alone (40% to 50% day +100 overall survival). These data suggest that the combination of high-dose steroids and defibrotide may be superior to defibrotide alone and warrant further investigation.

Successful Treatment of Influenza-Associated Acute Necrotizing Encephalitis in an Adult Using High-Dose Oseltamivir and Methylprednisolone: Case Report and Literature Review.

A case of influenza-associated acute necrotizing encephalitis (ANE) is described in an otherwise healthy adult. The patient was treated successfully with a combination of high-dose methylprednisolone and high-dose oseltamivir. The patient relapsed after discontinuing 150 mg twice daily oseltamivir but quickly improved and eventually recovered after reinitiation of high-dose oseltamivir for an additional 2 weeks. The clinical presentation, pathogenesis, and treatment of influenza-associated ANE is reviewed. The use of high-dose oseltamivir in combination with methylprednisolone may offer additional therapeutic benefit for this rare and poorly understood complication of influenza infection.

309 - Combination of High-Dose Methylprednisolone and Defibrotide for Veno-Occlusive Disease in Pediatric Hematopoietic Stem Cell Transplant Recipients

309 - Combination of High-Dose Methylprednisolone and Defibrotide for Veno-Occlusive Disease in Pediatric Hematopoietic Stem Cell Transplant Recipients

Sequential Therapy with Ofatumumab, High Dose Methylprednisolone and Lenalidomide Is a Safe and Effective Regimen for the Treatment of Previously Treated and Untreated CLL/SLL: The Hilo Trial

Background: With the introduction of new targeted drugs for the treatment of CLL, a new therapeutic paradigm is emerging where chemo-immunotherapy is being replaced by newer non-chemotherapy containing regimens with the goal to maintain long term responses while an oral drug is being administered. Based on demonstrated activity of ofatumumab (Ofa) and lenalidomide (len) as monotherapy, here we present the results of a sequential combination regimen consisting of high-dose methylprednisolone (HDMP) combined with Ofa, followed by consolidative therapy with Len in combination with Ofa.Methods: This is a Phase II, single institution, study involving pts with previously treated with relapse or refractory (R/R) disease or treatment naive (TN) CLL/SLL. During the first stage (cycles 1-3) patients (pts) were treated with a combination of HDMP 1000mg/m2 IV and Ofa 2000mg (300mg given week 1 then 2000mg for a total of 12 doses) IV infusion weekly x 4 doses in cycle 1 of a 28 day cycle, then every 2 weeks in cycle 2 and 3. During the second stage (cycles 4-12) pts were given Len 5-10mg daily (adjusted to CrCl) and Ofa 2000mg IV once every 8 weeks. Growth factor support was permitted at the discretion of the treating physician. Pts were assessed for response by iwCLL 2008 criteria (including CT assessment) after cycle 3 and 12 and allowed to continue on Len if they achieved CR, PR or SD. Primary end points were efficacy, adverse events (AEs) profile, and time-to-treatment failure (TTF)Results: Between 01/2012 and 05/2015, 73 pts (44 TN and 29 R/R) were enrolled in this study. Sixty-seven and 32 pts were evaluable at 3 months (40 TN and 27 R/R) and 12 months (22 TN and 10 R/R), respectively including response assessment. The median age was 63 (49 - 86) years and 67 (36-87) years for TN and R/R, respectively. For TN and R/R groups pts, 7 and 5 pts had 17pdel/TP53; and 31 and 20 pts were IgVH unmutated, respectively. Median number of prior treatments in the R/R cohort was 2(1-4). The median duration of treatment (DOT) was 14 (2 - 40) and 6 (1 - 40) months, respectively in the TN and R/R pts. Response rates are shown in table 1. With a median F/U for survivors of 18 and 35 months in the TN and R/R cohorts, respectively, 35 pts remain in the trial (31 TN and 4 R/R). The median TTF was 15 and 5.8 months in the TN and R/R cohort, respectively. Treatment was well tolerated in both arms with no grade 3/4 infusion reactions. Grade 3/4 treatment related hematological AEs were: neutropenia 50% and 82.8%, thrombocytopenia 9% and 20.7% and anemia 2.3% and 10.3% in the TN and R/R cohort, respectively. Grade 3 infections occurred in 6.8% and 41.4% pts in the TN and R/R cohorts, respectively. Three pts developed thromboembolism (2 PE and 1 DVT), all in the R/R cohort. None developed grade 3/4 tumor lysis syndrome or tumor flare. Three pts in each cohort underwent allo HSCT after a median of 3 cycles of therapy.Conclusion: Combination of ofatumumab, methylprednisolone and lenalidomide is an effective and well tolerated regimen in untreated or R/r CLL, including those with poor prognostic genetic features. This therapy may be used as salvage prior to allo-HSCT.Table 1TN, n=44R/R, n=29Assessment time, n3m, n= 4012m, n=223m, n=2712m, n=10CR n (%)1(2.3)3(6.8)01(10)PR n (%)31(77.5)17(77.3)14(51.9)7(70)SD n (%)8(20)2(4.5)13(48.1)2(10)PD n (%)002(3.7)0ORR n (%)32(80)20(90.9)14(48.3)8(80)NE n (%)4(10)22(50)2(8)15(62) DisclosuresPinilla-Ibarz:Teva: Consultancy, Speakers Bureau; Pfizer: Consultancy, Other: Consulting & Advisory Role, Research Funding, Speakers Bureau; Novartis: Consultancy, Other: Consulting & Advisory Role, Research Funding; ARIAD Pharmaceuticals, Inc.: Consultancy, Other: Consulting & Advisory Role, Research Funding; BMS: Consultancy, Honoraria, Other: Consulting & Advisory Role, Speakers Bureau. Off Label Use: Lenalidomide for CLL. Komrokji:Pharmacylics: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Incyte: Consultancy; Celgene: Consultancy, Research Funding. Locke:Kite Pharma: Other: Scientific Advisory Boards.

Transverse myelitis and acute motor sensory axonal neuropathy due toLegionella pneumophila: A case report

Guillain-Barré syndrome is a rapidly progressive symmetrical muscle weakness associated with acute inflammatory disease. Transverse myelitis (TM) is the inflammation of the spinal cord characterized by rapidly evolving muscle weakness in the lower extremities, defects in sensory level and sphincter dysfunction. Guillain-Barré syndrome, and TM association occurs very rarely in childhood. A 7-year-old girl presented with complaints of neck pain, spout-style vomiting, cough, shortness of breath, and acute paraparesis with sensory and sphincter disturbance. The patient was intubated because of increased respiratory distress. A positive direct fluorescein antigen test in bronchoalveolar lavage confirmed Legionella pneumophila infection. Imaging and neurophysiologic studies were diagnostic for TM with acute motor and sensory axonal neuropathy. She was treated with a combination of high-dose methylprednisolone and intravenous immunoglobulins, and we observed incomplete recovery. The presented case is the first child with concomitant TM and acute motor and sensory axonal neuropathy related to L. pneumophila infection.

Efficacy of Ofatumumab and High-Dose Methylprednisolone for the Treatment of Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Abstract 4619 Background:Ofatumumab is a fully-humanized anti-CD20 monoclonal antibody approved in refractory CLL. The combination of high-dose methylprednisolone (HDMP) and anti-CD20 monoclonal antibody rituximab has previously shown positive results in high-risk refractory CLL. Herein we report our institutional experience with the combination of ofatumumab and HDMP for the treatment of patients with relapsed or refractory CLL. Methods:Between October 2009 and June 2011, 10 consecutive patients with relapsed or refractory CLL received HDMP and ofatumumab at Moffitt Cancer Center. HDMP was dosed at 1 g/m2 IV weekly for 3 weeks every 28 days for two cycles, then monthly for 3 cycles. Ofatumumab was administered according to package insert instructions along with prophylactic antimicrobials. The primary endpoint was to evaluate response as defined by the updated National Cancer Institute Working Group Guidelines (NCIWG 2008). Secondary objectives were to assess treatment tolerance and toxicity. Descriptive statistics were used for baseline characteristics and response rates. Results:Eight of ten patients were male, with a median age of 60 years (range 43–81). All patients were previously treated with rituximab, and were intolerant to or failed fludarabine and/or alemtuzumab. The median number of prior treatments was 3.5 (range 1–5). Seven patients had high-risk prognostic markers including unfavorable cytogenetics or unmutated IgVH. Six patients had 17p deletion, 2 patients had 11q deletion, and 3 patients had an unmutated IgVH (6 patients had two prognostic markers). Eight patients were able to complete all planned treatments. One patient discontinued treatment due to worsening performance status and 1 patient discontinued treatment due to progressive disease. HDMP and ofatumumab were used as a bridge to allogeneic hematopoietic stem cell transplant in 4 patients. Based on NCIWG 2008 criteria, 2 patients had a partial response (PR), 1 patient had progressive disease (PD), and 6 patients had stable disease (SD). Five patients with stable disease had a clinical decrease of lymph nodes or a decrease in lymphocyte counts.Despite the use of prophylactic antimicrobials severe infectious complications occurred in 40% of patients. Infections included 1 patient with norovirus, 1 patient with cytomegalovirus viremia and a fusarium infection of the neck, 1 patient with aspergillus pneumonia, Pseudomonas aeruginosa bacteremia, and an Escherichia coli bacteremia, and 1 patient with a necrotizing pneumonia. Conclusion:This data demonstrates the benefit of HDMP and ofatumumab combination in patients with heavily pretreated CLL. The combination of ofatumumab and HDMP has a role as salvage therapy and as a bridge to allogeneic stem cell transplant. The incidence of infection was high despite the use of prophylactic antibiotics. Aggressive antibiotic prophylaxis is warranted including coverage for mould infections. Disclosures:Off Label Use: Ofatumumab in combination with high dose methylprednisolone for the treatment of relapsed/ refractory CLL. Pinilla-Ibarz:GSK: Speakers Bureau.

5.56 Ofatumumab in Combination with High-Dose Methylprednisolone as a Salvage Treatment for Heavily Pretreated or Refractory Patients with Chronic Lymphocytic Leukemia

Treatment options for relapsed / refractory or heavily pretreated patients with chronic lymphocytic leukemia (CLL) are limited, and these patients typically have a poor prognosis. We conducted a study to evaluate the combination of High-dose methylprednisolone (HDMP) with ofatumumab (HDMP-O) in patients who were not considered eligible to receive chemotherapy due to the presence of comorbidities, poor performance status, severe cytopenias and / or refractory status to fludarabine or alemtuzumab. Patients received HDMP 1 g/m2 IV daily × 3 every 28 days for three consecutive cycles, and ofatumumab 300 mg (dose 1) followed by 11 doses of 2,000 mg over a 6 month period, along with prophylactic antimicrobial therapy (trimethoprim-sulfamethoxazole 160/800 mg twice a day × 3 per week, fluconazole 100 mg/day and valganciclovir 900 mg/day). Eight patients were evaluated; all of them were males with progressive and symptomatic CLL. Median age was 69 years (range 49–78 years). The mean number of prior treatment regimens was 3.75, including four patients that had previously received HDMP and rituximab and two patients that underwent matched unrelated donor stem cell transplantation. All patients had been previously treated with rituximab, 75% of the patients were refractory to fludarabine and / or aletuzumab, and 88% had high-risk disease based on the presence of unfavorable cytogenetics (17p-, 11q-), unmutated IgVH status, or ZAP-70 expression. Bulky disease and splenomegaly were present in 62.5% of patients. All patients completed the planned therapy with no major side effects or toxicities. There was no evidence of myelosupression, and even patients with pancytopenia improved their peripheral blood counts. Response assessment based on the IW-CLL 2008 criteria showed an overall response rate of 50% (4 partial responses), 25% of patients had stable disease and the remainder showed progressive disease. The median time to progression in responders was 7 months. Overall survival 6 months after treatment was 65%. This study suggests that the combination of HDMP and Ofatumumab is a safe and effective salvage regimen for high-risk CLL patients who otherwise would not be candidates for additional treatment.

High dose methylprednisolone and rituximab is an effective therapy in advanced refractory chronic lymphocytic leukemia resistant to fludarabine therapy

The combination of high dose methylprednisolone and rituximab induces superior overall (93%) and complete (14%) response rates compared to high dose methylprednisolone alone (overall 43%, complete remission 0%) in heavily pre-treated chronic lymphocytic leukemia patients with advanced disease. Despite its efficacy the combination is not easily manageable because of the high rate of opportunistic infections.

High Dose Methylprednisolone and Rituximab Is an Effective Therapy in Advanced Refractory Chronic Lymphocytic Leukaemia Resistant to Fludarabine Therapy.

The management of refractory advanced chronic lymphocytic leukaemia (CLL) continues to pose a considerable challenge to the clinician. CLL patients who are refractory or become resistant to fludarabine containing regimens currently have a poor prognosis. High dose methylprednisolone (HDMP) has been shown to be an effective therapeutic option in patients who are resistant to fludarabine particularly those with bulky lymphadenopathy or refractory cytopenias who are unsuitable for alemtuzumab therapy. We have used HDMP in combination with the anti-CD20 monoclonal antibody, Rituximab, to treat 14 patients with advanced refractory CLL. Eight of fourteen patients were male. The median age was 62.5 years (range 30–71). Twelve patients had bulky lymphadenopathy with nodal masses greater than 5 centimetres in diameter. Nine patients had Binet stage C and the remainder were stage B. Autoimmune manifestations were present in five of the patients, and in one of them fludarabine therapy was contraindicated due to active autoimmune haemolysis. FISH analysis was performed to detect 17p, 11q and 13q deletions and showed 11q23 deletions in five patients. The overall response rate was 93% with a median progression free survival (PFS) of seven months. Two patients achieved a CR, another a nodular PR and 10 patients had a PR. Responses were seen in all 4 patients who had not responded to alemtuzumab as a single agent. Only one patient failed to respond. The median survival was 20 months. All five patients with 11q23 deletions responded, and the mean progression free survival in this subgroup was 10.5 months. These results compare extremely favourably with our own previous study (Thornton et al, 1998) that used HDMP alone in the management of advanced/refractory CLL where only 43% of patients responded and no patients achieved a CR. We have demonstrated that the combination of HDMP with rituximab is more effective than HDMP alone (p<0.01) in advanced refractory CLL. Although HDMP in combination with rituximab causes little or no myelosuppression, 6/14 patients (43%) developed opportunistic fungal or viral infections and this included fungal mould infections, fungal yeast infections and opportunistic viral infections. Three patients died of pulmonary fungal infections, although 2 of these patients had been retreated with alternative regimens. While the immunosuppressive effects of high dose steroids are well recognised, it appears that the addition of rituximab has made these patients more prone to opportunistic infections. In summary, HDMP in combination with rituximab is an effective rescue regime in purine analogue refractory CLL particularly in patients with bulky lymphadenopathy who are unsuitable for alemtuzumab, and in patients with 11q23 deletions.

Selektive Immunadsorption bei neurologischen Komplikationen eines systemischen Lupus erythematodes

Vasculitis of the nervous system is a rare cause of multifocal neurologic symptoms and may involve both the central and peripheral nervous systems. Typical symptoms include headache, encephalopathy with cognitive impairment and psychotic symptoms, epileptic seizures, and peripheral neuropathies. Here we report the case of a 71-year-old female presenting with Raynaud's syndrome and paresthesia of the feet. Several weeks later she was admitted to our hospital with a status epilepticus and complex partial seizures. On admission she had mild aphasia, distal paresis of the arms without sensory deficits, and disorientation with hallucinations. Cerebral MRI revealed small, multifocal infarctions in several arterial territories. Multiple cerebral artery stenoses were detected by ultrasound. Examination of the CSF was unremarkable. Serologic tests for autoimmune disorders detected Ro antibodies compatible with systemic lupus erythematosus or Sjögren's syndrome. A sural nerve biopsy revealed ischemic axonal neuropathy. During administration of i.v. methylprednisolone, the symptom progression stopped but dosages could not be tapered due to severe CNS symptoms (mental decline, disorientation, aphasia, hallucinations). Slow but sustained clinical improvement was achieved by immunoadsorption over 3 weeks followed by a combined high-dose immunosuppressive treatment with cyclophosphamide and prednisolone that paralleled a reduction in anti-Ro titers and normalization of cerebral blood flow velocities as detected by repeated transcranial Doppler sonography. Systemic vasculitis may present with multiple neurologic and psychiatric symptoms due to involvement of the central and peripheral nervous systems. After excluding systemic infection, immunosuppressive therapy should be started early. In our case a combination of high-dose methylprednisolone, immunoadsorption with elimination of Ro antibodies, and cyclophosphamide led to the patient's recovery.

Hypereosinophilic syndrome with DIC treated successfully with a combination of high-dose methylprednisolone and cyclosporin A

Hypereosinophilic syndrome with DIC treated successfully with a combination of high-dose methylprednisolone and cyclosporin A