The relationship between cost and the recommendation, refusal, and discontinuation of treatment for chronic myeloid leukemia and multiple myeloma in Japan: a cross-sectional exploratory survey.

AIMS: This study aimed to ascertain the number of patients with chronic myelogenous leukemia (CML) and transplant-ineligible patients with multiple myeloma (MM) not recommended by their physicians for optimal drug treatment or who refuse, discontinue, reduce, or skip treatment owing to cost in Japan. METHODS: A cross-sectional survey was conducted among hematologists, hematologic oncologists, and oncologists in Japan treating ≥1 patient with CML or ≥5 transplant-ineligible patients with MM per year. RESULTS: A total of 212 physicians participated: 105 treating patients with CML and 107 treating transplant-ineligible patients with MM. While treatment cost did not lead to non-optimal treatment most patients, physicians reported that they recommended non-optimal treatment to 6.53% of their patients with CML and 1.41% of their transplant-ineligible patients with MM, that 1.51 and 0.35% of their patients, respectively, refused treatment and that 1.97 and 0.71% discontinued treatment owing to treatment cost. However, no significant differences in the effect of treatment cost on recommendation, discontinuation, refusal, or reduction of treatment were observed. Non-recommendation of optimal treatment owing to treatment cost was most common for third-line CML and fourth-line transplant-ineligible MM treatment. Discontinuation due to treatment cost was most common in third-line treatment for both. CONCLUSION: Our results show that non-optimal treatment due to treatment cost occurs among some physicians in Japan for patients with CML and transplant-ineligible patients with MM, but it may be limited to a small percentage of patients. Further research is needed to identify the drivers of treatment decisions for physicians and patients, including those involving treatment cost.

Immunomodulation of bioactive gibberellin confers gibberellin-deficient phenotypes in plants.

Immunomodulation is a means to modulate an organism's function by antibody production to capture either endogenous or exogenous antigens. This method was applied to plants to repress the function of gibberellins (GAs), a class of phytohormones responsible for plant elongation, by anti-bioactive GA antibodies. Two different antibodies were produced in Arabidopsis as single-chain variable fragment (scFv) fused to green fluorescent protein (GFP) with four different subcellular localizations: endoplasmic reticulum (ER), cytosol, apoplastic space or the outer surface of the plasma membrane. When targeting scFv-GFP to ER, plants showed the highest accumulation of scFv-GFP, with binding activity, strong GFP fluorescence in ER-derived compartments and mild but clear GA-deficient phenotypes, including a smaller leaf size, delayed bolting, shorter inflorescence length and decreased germination. Plants expressing scFv-GFP in ER responded to exogenous GA(4) and contained 15-40 times greater endogenous GA(4) than wild-type plants. They also showed increased gene expression for GA3ox1, GA20ox1 and GA20ox2, but decreased expression for GA2ox1, which are feedback and feedforward regulated by GA signalling, respectively. These results suggest that the level of free functional GA(4) decreased when trapped in the ER with scFv to the extent that mild GA-deficient phenotypes were created. A dramatic increase in the total sum of GA(4) (free plus scFv-GFP bound) was detected as a result of the up-regulation of GA biosynthesis (feedback regulated), and a decrease in GA(4) catabolism as a result of protection by scFv-GFP binding. This study demonstrates that the use of immunomodulation to inhibit the action of bioactive GAs is an effective method of creating GA-deficient plants.