High-dose Steroid Treatment Research Articles

Efficacy of very high dose steroid treatment in a case of Landau-Kleffnersyndrome

Landau-Kleffner syndrome (LKS) is an acquired childhood aphasia associated with paroxysmal bitemporal electroencephalogram (EEG) abnormalities and, sometimes, clinical seizures. We report the case of a female aged 5 years 6 months who presented clinically with apparent hearing loss, deterioration in speech, and seizure activity over 12 days. The female had previous detailed speech/language assessments at 3 to 4 years of age due to articulation delay. LKS was diagnosed on EEG with bitemporal spike and wave activity during sleep. The patient was treated with high dose prednisolone 3mg/kg/day, intensive speech/language therapy, and followed a modified educational program. We recorded a marked regression in receptive and expressive language skills, as well as her speech, language, and cognitive profiles before and during treatment with prednisolone, during an 18-month follow-up period. The patient demonstrated an excellent clinical response highlighting the importance of a multidisciplinary approach to management of LKS.

Paradoxical worsening of tuberculosis in a heart–lung transplant recipient

We report on a heart-lung transplant recipient who presented with pulmonary tuberculosis (TB) 2.5 months after transplantation and then developed a paradoxical reaction after 4 months of adequate anti-TB treatment. She eventually recovered with anti-TB and high-dose steroid treatments. Using sequential bronchoalveolar lavages, we assessed the inflammatory response in the lung and investigated the alveolar immune response against a Mycobacterium tuberculosis antigen. The paradoxical reaction was characterized by a massive infiltration of the alveolar space by M. tuberculosis antigen-specific CD4(+) T cells and by the presence of a CD4(-)CD8(-) T lymphocyte subpopulation bearing phenotypic markers (CD16(+)/56(+)) classically associated with NK cells. This case report illustrates that even solid organ transplant recipients receiving intense triple-drug immune suppression may be able to develop a paradoxical reaction during TB treatment. Transplant physicians should be aware of this phenomenon in order to differentiate it from treatment failure.

Effect of Extracorporeal Photopheresis on Steroid Resistant Acute GVHD Refractory to High Dose Steroid Treatment

Background: The mortality of patients with steroid resistant acute graft-v ersus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is high due to multiple organ failure and infection. Recently, the use of extracorporeal photopheresis (ECP), which is believed to have a low risk of infection, has been applied for the treatment of GVHD. Methods: Of 23 patients who were steroid resistant acute GVHD that was resistant even to high dose steroid treatment as second-line treatment, 10 patients received ECP (ECP group) and 13 patients received a third-line treatment other than ECP (non-ECP group). The outcome including the response rate and survival for the ECP group and non-ECP group was analyzed. Results: The response rate of the ECP group including complete remission and partial remission, was 30%. The survival rate was 30% for the ECP group and 0% for the non-ECP group. The estimated mean survival time was 229.3±89.3 days for the ECP group and 41.8±14.6 days for the non-ECP group (P=0.028). Conclusion: ECP can be considered as a treatment option for the steroid resistant acute GVHD that

The Results of Periocular Injections of Triamcinolone for Thyroid Orbitopathy

Purpose: The aim of this study is to evaluate the effects and complications of periocular injections of triamcinolone acetonide in patients with thyroid orbitopathy who could not tolerate systemic corticosteroid therapy. Methods: Six patients with a mean age of 48.7 years showed symptoms of severe acute thyroid orbitopathy. They received four doses of 20 mg of triamcinolone acetonide via periocular injection into the inferotemporal orbital quadrant every 2 weeks. The response to treatment and the presence of adverse effects were evaluated retrospectively. Results: Three of six patients (50%) showed significant improvement in soft tissue swelling in both eyes. Only one patient (17%) showed improvement of proptosis. No patients showed improvement in diplopia and ocular motility. The mean thickness of the extraocular muscles measured by CT scan remained unchanged. Compressive optic neuropathy developed in one patient and resolved after intravenous high-dose steroid treatment. Two patients received radiation therapy for resistant inflammatory symptoms. One patient underwent extraocular muscle surgery. In one patient, there was no adverse effect at the injection site, except for a foreign body granuloma. Conclusions: Periocular triamcinolone injection could be effective for patients with thyroid orbitopathy in the acute inflammatory phase in reducing soft tissue swelling. The procedure showed no significant effect on exophthalmos or ocular motility.

Significant response of radiation induced CNS toxicity to high dose steroid administration

Treatment of radiation myelopathy remains a challenge. Supportive and rehabilitative therapy is the mainstay of treatment. This article describes a case of central nervous system (CNS) toxicity of radiation with a progressive improvement in the clinicoradiological picture following high dose steroid treatment. A female patient was admitted to the neurology department of our hospital 7 months after a course of radiotherapy in another centre for lingual epidermoid cancer. Neurological examination revealed a heavy spastic quadriplegia syndrome. On MRI examination, T2 weighted hyperintensities were observed in cerebral and cerebellar peduncles, periventricular regions and medulla spinalis at Th1-Th2 levels. The patient was treated with high dose methylprednisolone, 1 g day(-1) for 5 days (pulse therapy) followed by oral methylprednisolone 80 mg day(-1) for a week, tapered over 3 weeks. Within the first week of pulse therapy, she regained muscle strength of upper limbs against gravity. At the 2 year follow-up, MRI demonstrated obvious regression of the lesions in the medulla and cerebellum with disappearance of contrast enhancement. This case report is notable with the complete disappearance of MRI lesions at the 2 year follow-up after the treatment with high dose steroid.

Idiopathic Granulomatous Encephalitis Mimicking Malignant Brain Tumor

Idiopathic granulomatous encephalitis is a rare disorder of unknown etiology, undetermined treatment, and often grave prognosis. This article describes a 4-year-old female who presented with a single focal febrile convulsion followed a few weeks later by right-sided hemiparesis. A huge infiltrative cerebral mass tumor was found which proved to be a granuloma on histologic study. Despite a thorough evaluation, including tissue studies and search for an infectious agent, no etiology could be identified, and the final diagnosis was idiopathic granulomatous encephalitis. Recurrent resections and high-dose steroid treatment failed to control the process, and the patient died of disease 6 months after presentation. Evaluation and treatment of idiopathic granulomatous encephalitis should be aggressive, and the possibility of chemotherapy and perhaps even radiotherapy should be considered if there is no response to steroids.

Interpretation of the short Synacthen test in the presence of low cortisol-binding globulin: two case reports

Ten percent of serum total cortisol (TC) is unbound; the remainder is bound to cortisol-binding globulin (CBG) and, to a lesser extent, albumin. CBG concentrations can drop significantly, particularly in critical illness, resulting in a low TC although the free, active, cortisol may be normal or increased. In the context of a low CBG, the diagnosis of pituitary-adrenal insufficiency with measurements of TC is difficult. To remind clinicians of the difficulty in interpreting TC when the CBG is low, the circumstances when CBG concentrations may decrease and that measurement of CBG and calculation of the free cortisol index can help in the assessment of pituitary-adrenal reserve. We present two patients at risk of primary and secondary adrenal insufficiency with a poor response to 250 microg Synacthen. In both cases we confirmed low CBG concentrations but a normal free cortisol index (FCI), confirming normal pituitary-adrenal reserve. In case one, we have been able to avoid long-term steroid replacement therapy. We continue to reduce the steroid dose in case 2 but have been limited by the need for high-dose steroid treatment for exacerbations of the patient's airways disease. The use of TC in the assessment of the hypothalamic-pituitary-adrenal (HPA) axis may give rise to misleading results if the CBG concentration is low. The FCI may be a better marker of pituitary-adrenal reserve in these subjects. Clinicians should be cautious when interpreting abnormal cortisol results and we emphasize the importance of good clinical assessment.

Efficacy of very high dose steroid treatment in a case of Landau–Kleffner syndrome

Landau-Kleffner syndrome (LKS) is an acquired childhood aphasia associated with paroxysmal bitemporal electroencephalogram (EEG) abnormalities and, sometimes, clinical seizures. We report the case of a female aged 5 years 6 months who presented clinically with apparent hearing loss, deterioration in speech, and seizure activity over 12 days. The female had previous detailed speech/language assessments at 3 to 4 years of age due to articulation delay. LKS was diagnosed on EEG with bitemporal spike and wave activity during sleep. The patient was treated with high dose prednisolone 3mg/kg/day, intensive speech/language therapy, and followed a modified educational program. We recorded a marked regression in receptive and expressive language skills, as well as her speech, language, and cognitive profiles before and during treatment with prednisolone, during an 18-month follow-up period. The patient demonstrated an excellent clinical response highlighting the importance of a multidisciplinary approach to management of LKS.

Maternal corticosteroids to prevent intrauterine exposure to hyperthermia and inflammation: A randomized, double-blind, placebo-controlled trial

Intrauterine exposure to hyperthermia at term is associated with adverse neonatal neurologic outcomes. The objective of this study was to determine whether prophylactic maternal corticosteroid treatment prevents fetal exposure to hyperthermia and inflammatory cytokines after epidural analgesia. A 2-phase, randomized, institutional review board-approved, double-blind, placebo-controlled trial was performed. Term nulliparous women were enrolled at epidural placement. Patients with a temperature of >99.4 degrees F or with diabetes mellitus were excluded. In phase 1, 25 mg methylprednisolone (low dose) or placebo was administered every 8 hours. In phase 2, the treatment dose was increased to 100 mg every 4 hours (high dose). Our primary outcome was a rate of intrapartum fever of >100.4 degrees F. Secondary outcomes were fetal interleukin-6 levels and the rate of neonatal bacteremia. One hundred one patients were assigned randomly to placebo; 50 patients were assigned to the low-dose group, and 49 patients were assigned to the high-dose group. Treatment with the high dose resulted in a 90% reduction in maternal fever, compared with placebo and low dose therapy (2.0% vs 21.8% vs. 34.0%, respectively; P < .001). Neonatal sepsis evaluations were reduced significantly in the high-dose group (4.1% vs 17.8% vs 24%, respectively; P = .01), but the rates of asymptomatic bacteremia were increased (9.3% vs 0% vs 2.1%, respectively; P = .005). Median cord blood interleukin-6 levels were reduced with the high-dose steroid treatment, but this result was statistically significant only between the high-dose and placebo groups (24.0 +/- 38.5 vs 32.0 +/- 95.0 pg/mL, respectively; P = .02). Prophylaxis with high-dose corticosteroids significantly reduces fetal exposure to hyperthermia and inflammation. However, maternal high-dose corticosteroids increase the rate of neonatal asymptomatic bacteremia. Stress-dose corticosteroid use in labor should trigger consideration of a screening neonatal blood culture.

POEMS syndrome-related pulmonary hypertension is steroid-responsive

The POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal immunoglobulin, Skin changes) syndrome is a rare disease that entails a specific risk for pulmonary arterial hypertension. We report on 2 patients who suffered from POEMS syndrome and pulmonary arterial hypertension for whom a detailed hemodynamic pulmonary study was obtained before and after steroid treatment. Patient 1 had defined post-capillary pulmonary hypertension (PH) ascribed to an abnormally high cardiac output. Patient 2 suffered from severe pre-capillary PH. Under high-dose steroids treatment, clinical symptoms disappeared and PH assessment by sequential hemodynamic study showed a clear-cut improvement in both patients. First-line therapy should include corticosteroids in POEMS syndrome-related PH.

Acute eosinophilic pneumonia after allogeneic hematopoietic stem cell transplantation

A 55-year old woman with multiple myeloma was treated with hematopoietic stem cell transplantation (HSCT). She developed cutaneous and hepatic graft-vs-host disease (GVHD). Sixty-five days after HSCT, acute respiratory failure occurred. A thoracic computed tomography scan showed bilateral patchy infiltrates. Bronchoalveolar lavage revealed 40% eosinophils on differential cell count with no infectious pathogens. These findings were in favor of acute eosinophilic pneumonia. High-dose steroid treatment was started, which had a rapid and lasting favorable course. After HSCT, clinicians should be aware that acute eosinophilic pneumonia mimics infectious pneumonitis and can be associated with GVHD.

Steroid Complications in Patients with Acute Graft Versus Host Disease.

Background: High dose steroid treatment remains to be the first line therapy for acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Although effective in controlling aGVHD, high dose steroids can cause multiple serious complications which can result in increased morbidity and mortality.Purpose: Our aim was to determine the frequency of steroid induced complications and to analyze risk factors for steroid-myopathy in patients with AML who developed grade 2 aGVHD after allogeneic HSCT.Patients and Methods: Inclusion criteria were:1) AML/MDS patients who received allogeneic HSCT between 1/1996 and 12/20012) grade 2 aGVHD treated with at least 2mg/kg of methylprednisolone3) post transplantation overall survival at least 100 days.Steroid induced complications reviewed were: cataracts, headaches, mood swings, hypertension, gastritis, hyperglycemia, osteopenia, myopathy, avascular necrosis, edema, hypokalemia and infections. Pre- and post-transplantation characteristics analyzed as risk factors for steroid-myopathy were: age, gender, race, history of diabetes, body mass index, HLA types, steroid use after HSCT prior to grade 2 acute GVHD and duration of steroid use for acute GVHD. Logistic regression analysis was used for risk factor evaluation. Steroid-myopathy was defined as proximal muscle weakness, atrophy and myalgia in the absence of genetic, inflammatory or drug-induced etiologies other than steroid use.Results: 178 AML /MDS patients were transplanted during the study period. 70 patients (37 males and 33 females) with a median age of 43 (range, 21–66) were eligible for our study. Median duration of follow-up and median duration of steroid use after grade 2 aGVHD were 269 days and 127 days respectively. The number of patients and their frequency distribution of steroid induced complications were as follows: hyperglycemia, 43 (61.4%); hypertension, 35 (50%); cataracts, 10(14.3%); headaches, 7 (10%); mood swings,12(17.1%); gastritis, 7 (10%); myopathy, 32(45.7%); avascular necrosis, 1 (1.4%); edema, 22 (31.4%); hypokalemia, 52 (74.3%); bacterial infections, 55 (78.6%); viral infections, 39(55.7%); and fungal infections, 22(31.4%). For steroid-induced myopathy, male gender (RR=4.0, 95% CI=1.01–16.4, p=0.05), steroid use before acute GVHD grade II (RR=5.5, 95% CI=1.35–22.14, p=0.02) or steroid use more than 4 months after developing acute GVHD grade II (HR=6.4, 95% CI=1.38–29.94, p=0.02) were independent risk factors. 47 of 70 patients died with median overall survival of 10 months. 22 of 47 (46.8%) had steroid-myopathy and there was no increased mortality with steroid induced myopathy.Conclusion: Steroid therapy for aGVHD after allogeneic HSCT in AML/MDS patients is associated with frequent toxicities. The possibility of identifying prognostic factors for steroid toxicities support the study and development of strategies that may ameliorate or prevent steroid induced complications.

Longitudinal alteration of circulating dendritic cell subsets and its correlation with steroid treatment in patients with severe acute respiratory syndrome

In this study, we found that 74 patients with severe acute respiratory syndrome (SARS) exhibited a rapid, dramatic decrease in numbers of circulating myeloid and plasmacytoid dendritic cells (mDCs and pDCs) during the first 2 weeks of illness (5.3- and 28.4-fold reductions for mDCs and pDCs compared with 25 healthy individuals, respectively), with slow return to normal cell numbers during convalescence (weeks 5–7 of illness on average). In addition, numbers of circulating CD4 and CD8 T cells exhibited milder reductions (2.1- and 1.8-fold at week 1) and earlier return to normal at a mean of weeks 3 and 4, respectively. A significant inverse correlation was found between numbers of DC and T-cell subsets and high-dose steroid treatment. Our novel findings thus suggest that the acute SARS-coronavirus infection probably contributes to the initial reduction of DC and T-cell subsets in blood, and that high-dose steroid administration may subsequently exacerbate and prolong low expression of the cell subsets. These findings will aid the framing of further studies of the immunopathogenesis of SARS.

Bilateral Tumefactive Multiple Sclerosis Lesions

Tumefactive lesions are a rare form of multiple sclerosis (MS) presentation often provoking a diagnostic dilemma with brain tumour or abscess. We describe two cases of tumefactive demyelinating MS plaques and two different approaches. In the first patient the clinical and laboratory findings were consistent with MS, a diagnosis supported by the rapid response to high-dose steroid treatment. On the contrary, atypical clinical, imaging and laboratory findings in our second patient misled us to a diagnosis of a brain tumour. The diagnosis of MS was made after histopathological examination of the excised mass. Both our patients developed a second tumor-like demyelinating mass in the contralateral and almost homologous white matter two years after their first admission to our hospital. A brief review of the imaging diagnostic approach to tumor-like MS plaques and changes appearing in the contralateral and especially in the homologous white matter of MS patients is reported.

Thrombotic thrombocytopenic purpura in southern Turkey: a single-center experience of 29 cases

In this retrospective, nonrandomized study, we describe our experience in the management of 29 consecutive patients with thrombotic thrombocytopenic purpura (TTP) treated with a combined therapy of plasma exchange (PE) and steroids at a single center. We compared the effectiveness of high-dose steroids (20-25 mg/kg methyl prednisolone) as first-line treatment in combination with PE therapy with the combination of standard-dose steroids (1 mg/kg methyl prednisolone) and PE in adult patients with TTP. Clinical, laboratory data and treatment outcomes such as response rate, median time to recovery and survival were evaluated retrospectively. Overall (OR) and complete (CR) response rates were 69 and 52% respectively. Similar response rates were found in patients treated with pulse or conventional dose steroids; however, the median time to response was delayed in the high-dose methyl prednisolone (HDP) group. The median time from the initiation of symptoms to initiation of treatment was approximately 15 days (range: 0-30). Delayed treatment in our patients because of delayed referral to our center resulted in poor response to treatment. In all, four of 14 (27%) complete responders experienced relapses. The predicted relapse rate was 48% at a median of 30 months. All the relapses presented with a combination of thrombocytopenia and microangiopathic hemolytic anemia. This analysis showed that high-dose steroid treatment did not prove to be beneficial for TTP patients as firstline therapy combined with PE. Moreover, pulse steroid interventions might have resulted in delayed responses and our data suggest that initiation of treatment with PE should not be delayed.

Paradoxical Cyclosporine A Requirements in Pediatric Renal Transplants Receiving High‐Dose Steroids

The potent immunosuppressant cyclosporine A (CyA) is a mainstay of treatment in the renal transplant population. During episodes of acute allograft rejection, therapy also includes the pulse administration of high-dose steroids such as prednisone or methylprednisolone. Both steroids and CyA are metabolized by the CYP3A4 isoenzyme of the cytochrome P450 catalytic system. On a theoretical basis, high steroid concentrations during a rejection episode could competitively inhibit CyA metabolism, increasing its systemic concentration and decreasing its dose requirements. A database was compiled consisting of pediatric patients who had undergone an acute renal rejection event during the years 1993 to 2003. The severity of rejection events, as well as the CyA and prednisone dosing regimens used during rejection, were assessed using a comprehensive chart analysis. The presence or absence of additional medications that could potentially interact with CyA was also examined. Although some patients responded in the predicted manner, the authors also found that a subgroup of pediatric patients placed on highdose pulse steroid therapy for acute graft rejection required increased amounts of CyA to maintain therapeutic concentrations. The authors recommend monitoring of patients on high-dose steroids for paradoxical CyA requirements intermittently during high-dose steroid treatment to individualize CyA therapy appropriately during renal allograft rejection and thereby maximize efficacy while minimizing potential toxic side effects of CyA such as under-immunosuppression and organ rejection.

Sarcoidosis Presenting with Multiple Subcutaneous Nodules

We report an unusual case of subcutaneous nodular sarcoidosis in a 30-year-old man. The lesions were multiple, involving the eyelids, trunk, and extremities for one year. Chest X-ray and CT demonstrated an enlargement of many lymph nodes in the bilateral hilar region and infiltration in the peribronchial region. The patient was initially treated as extrapulmonary tuberculosis, in another hospital, but the treatment was in vain. After the biopsy of nodules from the skin and lung at VGH-Taipei, which showed chronic granulomatous inflammation and no fungus, bacteria, mycobacterium, or foreign body, using special stains, the final diagnosis was sarcoidosis. With high-dose steroid treatment, the skin lesions disappeared within one month. Sarcoidosis should be considered in the differential diagnosis of patients presenting with multiple subcutaneous nodules.

Children with acute myeloblastic leukemia presenting with extramedullary infiltration: the effects of high-dose steroid treatment

To evaluate whether children with acute myeloblastic leukemia (AML) presenting with extramedullary infiltration (EMI) have different clinical, morphologic features and prognosis from children without EMI, a 127 consecutive previously untreated children with AML were entered in this study. Fifty-one children (40%) had EMI at diagnosis and 27% of these showed multiple site involvement. Twenty-seven of 127 children (21%) presented myeloid tumors. No age related differences in the incidence of EMI was noted. However, analysis of clinical and biological features at diagnosis showed that WBC count ≥50×109l−1, hepatosplenomegaly >5cm, FAB AML-M4 and AML-M5 subtypes and CD13, CD14 expression of bone marrow (BM) leukemic cells (>20%) were more frequent in children with EMI. Two consecutive treatment protocols were used. In both protocols remission was achieved with combined high-dose methylprednisolone (HDMP) as a differentiating and apoptosis inducing agent with mild cytotoxic chemotherapy (low-dose cytosine arabinoside (LD Ara-C), weekly mitoxantrone and Ara-C or 6-thioguanine). Administration of short-course (4–7 days) HDMP (20–30mg/kg per day) alone resulted in a remarkable decrease in peripheral blood, BM blasts and in the size of EMI in responding patients. In both protocols, remission rate in patients with EMI was 71 and 80%, which was lower than that of the patients without EMI (87 and 89%). This may be attributed to the higher frequency of unfavorable features in children with EMI. However, in patients who presented with myeloblastoma and treated with a more intensive post-remission therapy (AML-94), the 4-year disease-free survival (DFS) and event-free survival (EFS) rates were not found to be significantly different from children who had no EMI (P>0.05). Whereas, the outcome of children who presented with gingival infiltration did not improve. In further studies, the prognostic significance of different localisation of EMI and the effect of addition of HDMP to cytotoxic chemotherapy should be explored in larger series.

Elevated intraocular pressure associated with steroid treatment for infantile spasms

Purpose To evaluate the ocular changes and medical and surgical therapy after high-dose systemic steroid treatment in babies with infantile spasm and hypsarrhythmia. Design Retrospective, noncomparative, interventional case series. Participants In 5 of the 9 (55%) babies with infantile spasm exposed to systemic corticosteroid treatment, an increase in intraocular pressure (IOP) and optic disc cupping was observed. Intervention Ophthalmic examination under mild sedation was conducted 3 to 4 weeks after initiation of systemic therapy. Antiglaucoma treatment was given to the patients found to have high IOPs and cup-to-disc ratio changes. Routine follow-up was continued until systemic therapy was completed. Main outcome measures Controlled IOP with a decrease in cupping damage after antiglaucoma therapy. Results Five patients required antiglaucoma treatment; one also underwent augmented trabeculectomy. Mean IOP decreased in this subgroup from 30.1 ± 9.5 mmHg to 15.4 ± 4.2 mmHg in the right eye ( P = 0.043) and from 32.6 ± 7.4 mmHg to 15.2 ± 1.8 mmHg in the left eye ( P = 0.043). Mean cup-to-disc ratio improved from 0.53 ± 0.2 to 0.37 ± 0.04 in the right eye ( P = 0.06) and from 0.57 ± 0.12 to 0.35 ± 0.05 in the left eye ( P = 0.042). Conclusions The rapid onset of IOP and cup-to-disc ratio changes in patients with infantile spasm and hypsarrhythmia treated by high-dose corticosteroids necessitates early and intensive monitoring to prevent anatomic ocular damage and visual impairment in the future.

The impact of antithymocyte globulin on short-term toxicity after allogeneic stem cell transplantation.

Antithymocyte globulin (ATG) is commonly used in allogeneic haematopoietic stem cell transplantation (HSCT). Little information is available, however, as to the optimal protocol for use and the side-effects occurring if ATG is administered in high daily doses (10-30 mg/kg). We report our experience with ATG Fresenius (ATG-F) in conditioning for allogeneic HSCT. During a period of 3 days, 47 patients received doses between 10 and 30 mg/kg either over 4 h preceded by 1-1.5 mg/kg prednisolone 30 min before the start of ATG-F (protocol A) or alternatively, over 12 h with 3-4 mg/kg prednisolone being administered before and 6 h after start of ATG (protocol B). During treatment with ATG-F, the side-effects observed included inflammation, disseminated intravascular coagulation, hyperdynamic circulation and renal dysfunction. Although these complications caused substantial morbidity, they were reversible within a few days. Side-effects were significantly more severe in patients treated according to protocol A than in those treated according to protocol B. As prolonged infusion of ATG-F does not reduce T cell clearance due to the long half-life of ATG-F, and since less cytokine release during conditioning might have beneficial long-term effects, we recommend administering ATG-F over 12 h preceded by high-dose steroid treatment.