Effect of L-Leucine Therapy on Hematopoietic Function in Elderly Myelodysplastic Syndrome Patients.

Patients with myelodysplastic syndrome (MDS) often require blood transfusion and anticancer therapy; however, elderly patients are intolerant to the associated side effects of anticancer therapy. Because L-leucine can be used to treat Diamond-Blackfan anemia, which is caused by defects in ribosomal protein (RP) genes, resulting in increased in vivo hemoglobin synthesis, it is possible that some MDS patients who have aberrations in their RP genes could also be effectively treated with L-leucine. In the present study, we investigated the effects of L-leucine on hematopoietic function (reticulocyte count), red blood cell count, and hemoglobin level in MDS patients. We administered L-leucine (1.8 g, twice daily, 3 d/week) with oral vitamin B6 supplements to a final cohort of eight MDS patients for 15 (interquartile range: 11-18) weeks. We assessed the patients at 10 ± 2 weeks after therapy initiation. Only the absolute reticulocyte count was affected, improving in 6/8 (75%) patients. The median absolute reticulocyte count was 3.5 × 104 (range: 2.7-6.4 × 104) cells/µL, an increase of 0.5 × 104 (range: 0.2-0.7 × 104) cells/µL. At 10 weeks, there was only one case of an improved hemoglobin level. Non-hematological adverse events of grade 3 were observed one raised triglycerides. These data suggest that L-leucine has little effect on MDS. However, it may contribute to the recovery of hematopoietic function, futher study be desired.

Influence of R-CHOP Therapy on Immune System Restoration in Patients with B-Cell Lymphoma.

OBJECTIVE: To assess the immunosuppressive effect of R-CHOP in patients with B-cell lymphoma at 2 years. METHODS: Parameters of humoral and cell-mediated immunity were assessed in 89 patients with diffuse large B-cell lymphoma or follicular lymphoma before and after 6-8 cycles of R-CHOP-14 or R-CHOP-21 regimen. RESULTS: Data on pre- and posttreatment serum IgG (sIgG) levels were available for all 89 patients, while the corresponding data on serum CD20+, CD3+, CD4+, and CD8+ lymphocyte counts were available in only 43. Median sIgG levels significantly decreased from 1,221 mg/dl (baseline) to 733 mg/dl (after chemotherapy) (p < 0.001). Although CD20+ and CD4+ cell counts decreased (p < 0.001), no significant effect of chemotherapy on CD3+ and CD8+ cell counts was observed. CD20+ cell counts were restored to baseline levels at the 12-month follow-up. sIgG levels and CD4+ cell counts were not completely restored at 24 months, indicating a sustained immunosuppressive effect of R-CHOP in these patients. The incidence of infections over the 2-year period was 16.3-23.6%. CONCLUSION: The immunosuppressive effect of R-CHOP in newly diagnosed cases of B-cell lymphoma tends to persist for >2 years, although sIgG levels were restored more quickly than CD4+ cell counts.

Evaluation of a method for calculating carboplatin dosage in DeVIC ± R therapy (combination therapy of dexamethasone, etoposide, ifosfamide and carboplatin with or without rituximab) as a salvage therapy in patients with relapsed or refractory non-Hodgkin lymphoma.

PURPOSE: Several studies have evaluated the utility of extrapolating the Calvert formula in calculating carboplatin (CBDCA) dosages in solid tumours; however, data regarding haematological cancers are less. Therefore, we conducted a preliminary study of the utility of extrapolating the Calvert formula in calculating CBDCA dosages for DeVIC ± R therapy. METHODS: A retrospective study on 57 non-Hodgkin lymphoma patients who had received DeVIC ± R therapy was conducted. The area under the curve (AUC) of CBDCA was back-calculated from actual dosages using the Calvert formula. Patients were divided into two groups according to an AUC ≥ 4 or an AUC < 4, respectively. The Revised Response Criteria of the International Working Group and CTCAE version 4.0 were used for assessing the treatment efficacy and adverse events, respectively. RESULTS: The use of AUC instead of body surface area had greater utility in calculating CBDCA dosage, with a response rate of greater than 50 % in patients receiving DeVIC ± R therapy with an AUC ≥ 4 for CBDCA. The response rate of the AUC ≥ 4 group was significantly higher than that of the AUC < 4 group. Decreased platelet and neutrophil counts of grade ≥3 occurred at higher rates in the AUC ≥ 4 group. CONCLUSION: The extrapolation of the Calvert formula has utility in calculating the CBDCA dosage for DeVIC ± R therapy, and therapeutic efficacy was increased by maintaining the AUC of CBDCA at ≥4.

Titanocene(II)-promoted, one-pot, three-component coupling of thioacetals, alkynyl sulfones, and carbonyl compounds: highly stereoselective formation of tert-homopropargyl alcohols.

Titanocene alkylidene complexes, generated by desulfurizative titanation of thioacetals with Cp2Ti[P(OEt)3]2, reacted with alkynyl methyl sulfones to produce organotitanium species, which gave tert-homopropargyl alcohols with high diastereoselectivity on treatment with aromatic and alpha,beta-unsaturated ketones.