Pomalidomide desensitization in a patient hypersensitive to immunomodulating agents.

Despite progressive treatments with tandem stem-cell transplantation, patients with incurable myeloma eventually succumb to relapsed or refractory disease if left untreated. Promising agents such as proteasome inhibitors and immunomodulating imide drugs (imids), including the newer-generation agent pomalidomide, in combination with lower-dose dexamethasone, have been shown to be effective and to significantly improve and prolong survival in pretreated patients. Although the incidence of pomalidomide hypersensitivity reaction (hsr) in this class of drugs is not as well known, we have documented cutaneous toxicity (grade 3 by the Common Terminology Criteria for Adverse Events, version 4) in 2 separate cases (not yet published). Because the imids are chemically, structurally, and pharmacologically similar, it is not unreasonable to consider possible cross-reactivity in pomalidomide recipients who developed hsr when receiving previous lines of imids. As a patient's advocate, it is only prudent to provide a responsible, and yet practical, means to better address cross-sensitivity for patients. Intervention with the use of a rapid desensitization program (rdp) as a preventive measure should be introduced before initiating pomalidomide. Such a proactive measure for the patient's safety will ensure a smooth transition into pomalidomide treatment. A hsr can be either related or non-related to immunoglobulin E. As imids become an essential treatment backbone for myeloma and other plasma-cell diseases, an increasing number of patients could experience skin and other life-threatening toxicities, resulting in unnecessary discontinuation of these life-prolonging agents. An extemporaneously prepared pomalidomide suspension developed at our centre enables patients to undergo rdp safely. Patients enjoy a good quality of life and clinical response after the rdp procedure.

Venous thromboembolism prevention during asparaginase-based therapy for acute lymphoblastic leukemia.

BACKGROUND: Venous thromboembolism (vte) is a recognized complication in patients treated with asparaginase-containing chemotherapy regimens; the optimal preventive strategy is unclear. We assessed the safety and efficacy of prophylaxis using low-dose low molecular weight heparin in adult patients with acute lymphoblastic leukemia in complete remission treated with an asparaginase-based post-remission chemotherapy regimen. METHODS: As part of the intensification phase of the Dana-Farber Cancer Institute 91-01 regimen, asparaginase was administered weekly to 41 consecutive patients for 21-30 weeks; these patients also received prophylaxis with enoxaparin 40 mg daily (60 mg for patients ≥80 kg). Outcomes were assessed against outcomes in a comparable cohort of 99 patients who received the same chemotherapy regimen without anticoagulation prophylaxis. RESULTS: The overall rate of symptomatic venous thrombosis was not significantly different in the prophylaxis and non-prophylaxis cohorts (18.92% and 21.74% respectively). Among patients receiving prophylaxis, vte occurred in higher proportion in those who weighed at least 80 kg (42.86% vs. 4.35%, p = 0.0070). No major bleeding complications occurred in the prophylaxis group (minor bleeding: 8.1%). CONCLUSIONS: Prophylaxis with low-dose enoxaparin during the intensification phase was safe, but was not associated with a lower overall proportion of vte.

Human albumin eye drops as a therapeutic option for the management of keratoconjunctivitis sicca secondary to chronic graft-versus-host disease after stem-cell allografting.

BACKGROUND: Keratoconjunctivitis sicca from chronic graft-versus-host disease (cgvhd) after allogeneic stem cell transplantation is common, leading to severe corneal damage and blindness if not treated. We retrospectively examined the efficacy and safety of pooled human albumin eye drops (haeds) for symptom relief in 40 stem-cell transplantation patients after other alternatives had failed. METHODS: The Common Terminology Criteria for Adverse Events (version 4.0) and the cgvhd grading scale were used to compare response in the patients during January 2000 and July 2013. In addition, on days 1 and 30, the haeds were subjected to quality assurance testing for sterility, oncotic pressure, albumin measurement, viscosity, pH, and purity by protein electrophoresis. RESULTS: Use of haeds resulted in symptom relief for 37 patients (92.5%); 3 patients (7.5%) failed to improve with use of haeds (p ≤ 0.0001). Of the 37 patients having symptom relief, 7 (19%) improved from grade 3 to no dry eye symptoms. Proportionately, post-treatment symptom improvement by two grade levels, from 3 to 1 (70%), was significantly higher than improvement by one grade level, from 3 to 2 (11%) or from 2 to 1 (19%, p ≤ 0.0001). Time to symptom relief ranged from 2 weeks to 28 weeks. Of the 40 patients, 38 (95%) had no adverse reactions. Days 1 and 30 quality assurance testing results were equivalent. CONCLUSIONS: Complications of keratoconjunctivitis sicca were well managed and well tolerated with haeds when other remedies failed. Quality assurance testing confirmed that haeds were safe and stable in extreme conditions.

The management of spinal metastasis in children.

OBJECTIVE: To seek an optimal treatment plan from the results of treatment for metastatic disease of the spine in children. DESIGN: An 8-year retrospective study of children with metastatic disease of the spine. Imaging studies were reviewed and treatment modalities analysed. SETTING: The divisions of pediatric orthopedics and pediatric neurosurgery at the Children's Hospital of Eastern Ontario, Ottawa. PATIENTS: All children seen between April 1980 and December 1987 who had lesions metastatic to the spine by hematogenous or direct extension. There were 20 children (15 boys, 5 girls) with a mean age at the time of diagnosis of 9.5 years. Follow-up ranged from 2 weeks to 108 months. One child was lost to follow-up. INTERVENTIONS: Eleven children underwent laminectomy and decompression. Of the 14 neurologically compromised children, 5 received chemotherapy and radiotherapy and 9 received chemotherapy, radiotherapy and surgery. MAIN OUTCOME MEASURES: Type of metastatic lesion, vertebrae involved and response to therapy. RESULTS: Vertebrae involved with metastases were as follows: cervical (3), thoracic (5), lumbar (8) and multilevel (2). Meninges were involved in 2 cases. The most common causes of metastatic spinal involvement were neuroblastoma (4 cases) and astrocytoma (6 cases). Pathologic fractures occurred in 4 children and kyphoscoliosis in 4. Spinal cord paresis developed in 14 of the 20 children. Of the 6 children who survived from 48 to 108 months, 5 had tumours of neural origin, 4 being astrocytomas. Children with neuroblastoma or leukemic infiltration had a good initial response to chemotherapy. Five of the 6 surviving children had astrocytomas, and 5 were treated by surgical decompression. CONCLUSIONS: Metastatic disease of the spine in children secondary to astrocytoma should be treated aggressively, but from the experience gained from this study it is impossible to devise a rigid treatment plan for each type of metastatic tumour. The choice of chemotherapy, radiotherapy or surgery depends on the type of tumour, the age of the child and whether or not the spinal cord is compromised.