Dynamics of virus-specific T cell immunity in pediatric liver transplant recipients.

Immunosuppression following solid organ transplantation (SOT) has a deleterious effect on cellular immunity leading to frequent and prolonged viral infections. To better understand the relationship between posttransplant immunosuppression and circulating virus-specific T cells, we prospectively monitored the frequency and function of T cells directed to a range of latent (CMV, EBV, HHV6, BK) and lytic (AdV) viruses in 16 children undergoing liver transplantation for up to 1 year posttransplant. Following transplant, there was an immediate decline in circulating virus-specific T cells, which recovered posttransplant, coincident with the introduction and subsequent routine tapering of immunosuppression. Furthermore, 12 of 14 infections/reactivations that occurred posttransplant were successfully controlled with immunosuppression reduction (and/or antiviral use) and in all cases we detected a temporal increase in the circulating frequency of virus-specific T cells directed against the infecting virus, which was absent in 2 cases where infections remained uncontrolled by the end of follow-up. Our study illustrates the dynamic changes in virus-specific T cells that occur in children following liver transplantation, driven both by active viral replication and modulation of immunosuppression.

Specific abnormalities versus number of abnormalities and cytogenetic scoring systems for outcome prediction after allogeneic hematopoietic SCT for myelodysplastic syndromes.

Newer cytogenetic scoring systems for myelodysplastic syndromes (MDSs), like cytogenetic stratification of the revised international prognostic scoring system (IPSS-R) or monosomal karyotype, may also improve outcome prediction after hematopoietic SCT (HCT). We compared the prognostic value of specific cytogenetic abnormalities, IPSS-R karyotype and monosomal karyotype for HCT outcome in 98 patients with MDS and AML post MDS. Higher-risk IPSS-R karyotype, 3q21q26 and transformation to AML before HCT were associated with increased cumulative incidence of relapse (CIR), whereas OS was adversely influenced by del 5q/-5, abnormalities of chromosomes 11 and 17 and cytogenetic IPSS-R very poor category. Karyotype with ⩽2 abnormalities and no abnormalities of chromosomes 3, 5, 7, 11 and 17 was an independent prognostic factor of lower CIR (hazard ratio (HR)=0.2, P=0.01) and longer OS (HR=0.5, P=0.03). In conclusion, some specific cytogenetic abnormalities and high cytogenetic complexity, as reflected by IPSS-R very poor karyotype, rather than monosomal karyotype, were associated with higher CIR and shorter OS after HCT. Conversely, results were encouraging in patients lacking those abnormalities, who may be very good candidates for HCT.

Continuous 24-hour infusion of folinic acid does not increase the response rate of 5-fluorouracil but only the toxicity.

Twenty-four patients with advanced colorectal cancer received two cycles of combination chemotherapy consisting of mitomycin 10 mg/m2 for 5 days continuous infusion and allopurinol 300 mg x 3/day p.o. for 21 days. Two patients responded partially following the two cycles of chemotherapy. Additionally, all patients received folinic acid 200 mg/m2 for 5 days as a continuous infusion. None of the nonresponders responded to the addition of folinic acid, on the contrary toxicity was increased and 2 toxic deaths were reported. We conclude that continuous infusion of folinic acid added to the combination of mitomycin and 5-fluorouracil does not improve the response rate but only enhances toxicity.

Prevention of tissue necrosis due to accidental extravasation of cytostatic drugs by a conservative approach.

The purpose of the present study was to evaluate comparatively the effectiveness of a conservative approach to treatment, using two therapeutic schedules (with and without sodium thiosulfate (ST), so as to minimize necrosis due to drug extravasation and to avoid the need for reconstructive surgery. The 63 patients entered into this study were separated into two groups; these in group A were treated with hydrocortisone and dexamethasone, and these in group B received the combination plus ST. In both groups, the drugs that had extravasated included doxorubicin, epirubicin, vinblastine, mitomycin C. The healing time varied with the different drugs used and was proportional to the extent of extravasation and to the time at which therapy was begun. The mean healing time for group B, which received ST was about half that for group A, which did not. We conclude that the application of conservative measures during chemotherapy may prevent tissue necrosis due to drug extravasation and the subsequent need for reconstructive surgery. The administration of ST can help in the achievement of this goal.

Decreased oral toxicity with the local use of allopurinol in patients who received high dose 5-fluorouracil.

5-Fluorouracil (5FU) is the most effective drug in gastrointestinal cancer. Mucositis and bone marrow toxicity are the two major limiting side effects. In our effort to reduce mucositis we administered Allopurinol mouthwash in 42 patients who had experienced oral mucositis during prior treatment with 5FU. In all patients significant reduction of oral toxicity was noticed as well as prolonged pain relief.

Conservative approach to the treatment of chemotherapy-induced extravasation.

One of the local complications of certain chemotherapeutic agents is tissue necrosis resulting from extravasation. The purpose of this study was to evaluate the effectiveness of a conservative approach to treatment in order to minimize necrosis and the need for reconstructive surgery. Fifty-three patients entered this study. Twenty-one had old lesions while 32 had recent extravasations. Drugs responsible for the extravasations were doxorubicin, epirubicin, vinblastine, mitoxantrone, and mitomycin C. The basis of treatment was betamethasone ointment, which was applied to the lesion with a tight elastic bandage and was replaced every 12 hours for the first 2 days and then every 24 hours until complete healing. For old lesions a keratolytic ointment was initially applied, whereas in the new lesions multiple subcutaneous injections with hydrocortisone solution preceded the application of betamethasone ointment. None of our patients developed tissue necrosis and sloughing that necessitated surgery. All lesions healed in patients. Healing time varied with the different drugs used and was proportional to the extension of extravasation and to the time when therapy was begun. We conclude that the application of conservative measures in extravasated areas from chemotherapy may avoid tissue necrosis and reconstructive surgery.

Comparison of antiemetic activity of chloropromazine and high doses of metoclopramide in cisplatin-based chemotherapy.

High dose metoclopramide and different phenothiazines are widely used antiemetics in cancer patients receiving chemotherapy. In a prospective randomized study we compared the antiemetic efficacy of high dose metoclopramide (M) and chloropromazine (C). We also tested the role of dexamethasone (D) when combined with either of these drugs. A total of 165 patients were randomly allocated to 5 groups with 33 patients in each group. Group A received only M, group B: M + D, group C: C + D, group D: M + D + C and group E: M + C. All patients received combination chemotherapy with cisplatin for the first time and were evaluated only once in order to exclude anticipatory nausea and vomiting. Patients in group C had less antiemetic protection than the other groups (p less than 0.001). Groups A, B, D, E, had more or less equal antiemetic efficacy, although the efficacy in group B was somewhat better; this difference was not statistically significant. Side-effects were minimal. Chloropromazine seemed to protect patients who received metoclopramide from extrapyramidal manifestations. In conclusion the results suggest that high dose metoclopramide has a better antiemetic effect than chloropromazine, dexamethasone is a helpful adjuvant drug when used in combination with an effective antiemetic agent, and chloropromazine and dexamethasone may prevent the extrapyramidal side-effects that can occur when metoclopramide is used as single antiemetic drug.