Efficacy and Safety of Thalidomide in Crohn’s Disease Patients with Perianal Fistula and Abscess

Background Medical therapies of parianal Crohn’s disease (CD) are limited. Thalidomide is an effective medical therapy to alleviate disease activity of CD. However, the effects and safety of thalidomide in the treatment of perianal fistula and abscess was not evaluated. Methods This retrospective cohort study was performed at a tertiary referral centre and recruited 73 patients with perianal CD who received thalidomide (50–100 mg) daily for 1 year. Data collected included demographics, medications, and disease behaviour. Clinical assessment of CD was conducted using the Crohn’s Disease Activity Index (CDAI), and perianal lesions were evaluated using the Fistula Drainage Assessment index and Perianal Disease Activity Index (PDAI). At the same time, the occurrence of adverse effects was recorded during treatment. Wilcoxon's signed-rank test and Student’s t-test were used to analyse the data. Results The CDAI score and laboratory indices were significantly lower after thalidomide treatment than at baseline (all P < 0.01). The value of PDAI was significantly lower in patients with symptomatic perianal abscess after thalidomide treatment than at baseline (10 [6.25, 10] versus 2.5 [1, 3.75]; P = 0.05). PDAI was also significantly reduced in all patients treated with thalidomide whether with or without perianal abscess drainage (all P < 0.05). The rates of responsive patients were similar between the thalidomide group and thalidomide combined with azathioprine group (72.73% [8/11] and 84% [21/25], respectively; P = 0.65). In total, 31% (24/77) of patients experienced adverse events, and interventions were required in 15 patients to reduce or eliminate discomfort from adverse events. Four patients discontinued thalidomide due to adverse effects. Side effects (rash, diarrhoea, peripheral neuropathy, somnolence, constipation, and numbness) were mild and mostly transient. Conclusions Thalidomide is effective in inducing clinical remission and response in CD patients with perianal fistula and abscess with or without abscess drainage. Thalidomide in combination with azathioprine is also effective in these patients. Low-dose thalidomide is proven to be effective and safe in treating perianal CD patients.

Efficacy of Thalidomide Treatment in Children With Transfusion Dependent β-Thalassemia: A Retrospective Clinical Study

Background: Thalidomide has been reported as a promising treatment for reducing transfusion volume in adults with β-thalassemia. However, the evidence about the safety and efficacy of thalidomide on children with transfusion dependent β-thalassemia (TDT) is scarce.Methods: Seventy-seven children with TDT treated with thalidomide at least for 6 months were included and retrospectively analyzed. Oral dose was started at 2.5 mg·kg-1·d-1. Blood volume for maintenance of hemoglobin above 90 g·L-1 compared with pre-treatment volume is the evaluation index for response.Results: After the sixth month treatment, 51/77 (66.2%) maintained Hb over 90 g·L-1 without transfusion. Adverse events were reported in 48 (63.2%) patients. Age, sex, genotype category, dosage, and transfusion interval before thalidomide treatment were not correlated to treatment response. The AUC was 0.806 for the HbF at the third month of treatment in predicting probability of major responders at the sixth month treatment. Based on Youden’s index algorithm in the ROC curve, 47.298 g·L-1 was the optimal cut-off value of the HbF at the third month of treatment in predicting major responders at the sixth month treatment, with sensitivity of 67.5% and specificity of 93.3%.Conclusions: The dose of thalidomide between 2.5 mg·kg-1·d-1 and 3.6 mg·kg-1·d-1 is effective in TDT children. Severe side effects are uncommon. HbF concentration of 47.298 g·L-1 at the third month is recommended as the predictor for further major responders.

Efficacy of thalidomide treatment in children with transfusion dependent β-thalassemia: a retrospective clinical study

Background Thalidomide has been reported as a promising treatment for reducing transfusion volume in adults with β-thalassemia. However, the evidence about the safety and efficacy of thalidomide on children with transfusion dependent β-thalassemia (TDT) is scarce. Methods Seventy-seven children with TDT treated with thalidomide at least for 6 months were included and retrospectively analyzed. Oral dose was started at 2.5 mg•kg-1•d-1 Blood volume for maintenance of hemoglobin above 90 g•L-1 compared with pre-treatment volume is the evaluation index for response. Results After the sixth month treatment, 51/77 (66.2%) maintained Hb over 90 g•L-1 without transfusion. Adverse events were reported in 48 (63.2%) patients.Age, sex, genotype category, dosage and transfusion interval before thalidomide treatment were not correlated to treatment response. The AUC was 0.806 for the HbFat the third month of treatment in predicting probability of major responders at the sixth month treatment. Based on Youden’s index algorithm in the ROC curve, 47.298 g•L-1 was the optimal cut-off value of the HbFat the third month of treatment in predicting major responders at the sixth month treatment, with sensitivity of 67.5%, specificity of 93.3%. Conclusions The dose of thalidomide between 2.5 mg•kg-1•d-1to 3.6 mg•kg-1•d-1 is effective in TDT children. Severe side effects are uncommon. HbF concentration of 47.298 g•L-1 at the third month is recommended as the predictor for further major responders.

Adherence to thalidomide in patients with multiple myeloma: A cross-sectional study in a Brazilian metropolis

Purpose The treatment of multiple myeloma (MM) has advanced with the introduction of immunomodulators (IMiDS). Thalidomide is the IMiD available in Brazil with free access to MM patients. Adherence to treatment with IMiDs is essential for a successful therapy. The study proposed to describe adherence to thalidomide treatment in patients diagnosed with MM in onco-hematological outpatient clinics. Methods This is a cross-sectional study with patients over 18 years of age diagnosed with MM undergoing thalidomide treatment. Adherence was measured by the Proportion of Days Covered (PDC), which is an indirect method of measuring adherence that uses database-related medication dispensing information. Patients with PDC ≥90 were classified as adherent. The association between adherence and independent variables was assessed in univariate and multivariate analyses using logistic regression. Results A total of 65 patients with a median age of 62.6 years were identified. The median PDC was 93.7%. The frequency of adherence to thalidomide was 56.9%. Adherence to thalidomide showed a negative association with hospitalization in the last 12 months (OR = 0.202; 95% CI = 0.060–0.687) and with higher schooling (OR =0.161; 95% CI = 0.039–0.667) and a positive association with higher income (OR = 5.115; 95% CI = 1.363–19.190). Conclusion Most patients from onco-hematological outpatient clinics in a metropolitan region of southeastern Brazil showed high adherence to thalidomide, which was independently associated with higher income, hospitalization, and higher schooling. More studies are required to understand better the determinants of adherence to thalidomide in the country.

Thalidomide Reduces Vascular Endothelial Growth Factor Immunostaining in Canine Splenic Hemangiosarcoma

Hemangiosarcomas (HSA) are common neoplasms of dogs that often metastasize and are typically fatal. Recently it was demonstrated that thalidomide extends the survival time of dogs with HSA, potentially due to thalidomide-induced inhibition of vascular endothelial growth factor (VEGF) production by the neoplastic cells. To investigate this, immunostaining was used to evaluate VEGF within HSA metastases that developed after thalidomide treatment. The immunostaining was then compared to VEGF immunostaining in primary tumors from the same dogs prior to treatment with thalidomide and in metastatic tumors from untreated dogs with splenic HSA. Immunostaining was scored from 1 to 4 for each sample. Immunostaining in the metastatic lesions that had been treated with thalidomide had a mean immunostaining score of 1.4 which was significantly lower than the mean score in the corresponding primary splenic HSA (3.8, p = 0.02) and in metastases from untreated dogs (3.5, p = 0.02). This supports the hypothesis that thalidomide prolongs survival time in dogs with HSA due to inhibition of VEGF production by the neoplastic cells. As VEGF remained visible within HSAs exposed to thalidomide, additional treatments to inhibit VEGF production may further prolong survival times of dogs with these common canine neoplasms.

Response to immunomodulatory drug-based regimens in heavily pretreated patients with recurrent/refractory adult Langerhans cell histiocytosis

Purpose: Langerhans cell histiocytosis (LCH) is a clonal histiocytic neoplasm and, because of its rarity in adults, there is no standard treatment for adult LCH. Immunomodulatory drugs (IMiDs) have been used to treat patients with low risk recurrent/refractory LCH but their effectiveness in adult LCH patients is unclear.Methods: We retrospectively evaluated the response rate to IMiDs-based regimens in ten heavily pretreated recurrent/refractory adult LCH patients at Peking Union Medical College Hospital.Results: A total of 10 patients (four males and six females) were included in this study. Median age at diagnosis was 33 years (range, 28–54 years). All patients had multisystem involvement and the median number of organs involved was 5 (range, 5–7). Seven patients had high risk organs involved, including seven patients with liver involvement and one with spleen involvement. All 10 patients had received at least one chemotherapy before the IMiDs-based regimen. The median number of previous lines of chemotherapy was 2 (range, 1–4). Eight patients received thalidomide, dexamethasone and cyclophosphamide, and two patients received lenalidomide and dexamethasone. The median time that patients received thalidomide treatment was 15 months and the duration of the two patients on lenalidomide regimen was 3 months and 12 months separately. Treatment responses in eight recurrent LCH patients included non-active disease in one patient and regressive disease in seven patients. The two refractory patients who had progression during the last treatment had stable disease after IMiDs therapy. During a median 15-months follow-up period, no disease reactivation or death was observed.Conclusions: IMiDs combined with dexamethasone and cyclophosphamide, may be a salvage therapy for recurrent/refractory adult LCH patients.