Impact of rituximab and half-dose CHOP as primary therapy for untreated symptomatic Waldenström Macroglobulinemia: review of a combined regimen of rituximab with an alkylating agent

BACKGROUND: Waldenström Macroglobulinemia (WM) is a rare subtype of indolent B-cell lymphoma, and prospective randomized studies on WM are scarce. The R-CHOP therapy [rituximab (R), cyclophosphamide, hydroxy-doxorubicin, vincristine, and prednisone] is a popular and recommended regimen for primary therapy, prescribed by several treatment guidelines for WM. However, treatment with R-CHOP is accompanied by severe myelosuppression and high rates of peripheral neuropathy. Therefore, we retrospectively evaluated the efficacy and toxicity of half-dose CHOP combined with R as a primary therapy for WM. METHODS: Patients with untreated symptomatic WM, treated at the Disaster Medical Center between April 2011 and September 2016, were retrospectively analyzed after administration of 6 cycles of half-dose R-CHOP for every 3 weeks. The response, median time to response, best response, progression-free survival, overall survival, and toxicities were evaluated. RESULTS: Of the 20 WM patients analyzed, 16 (80%) received half-dose R-CHOP without vincristine, and 13 (65%) responded to the treatment. With a median follow-up duration of 26.3 months, the 2-year progression-free survival and 2-year overall survival rates were 70 and 93.3%, respectively. The median time to response and best response were 6 and 9.9 weeks, respectively. Grade 3/4 leukocytopenia, neutropenia, febrile neutropenia, and Grade 1 peripheral neuropathy developed in 32, 37, 0, and 21% of patients, respectively. CONCLUSION: The half-dose R-CHOP is an effective and well-tolerated primary therapy for WM. To the best of our knowledge, this is the first study reporting the use of a reduced-dose R-CHOP regimen for the primary treatment of WM.

Clinical Efficacy of Reduced Dose GnRH Agonist Long Protocol for Controlled Ovarian Hyperstimulation in IVF-ET Patients with High Basal Serum FSH Level / 대한산부인과학회잡지

OBJECTIVE: To evaluate the clinical efficacy of half-dose and further reduced dose GnRH agonist long protocols for controlled ovarian hyperstimulation (COH) in in vitro fertilization and embryo transfer (IVF-ET) patients with high basal serum FSH level. METHODS: One hundred and two IVF-ET cycles performed in 84 infertile patients with high basal serum FSH level (FSH>10.0 mIU/mL) were included in this retrospective study. Study subjects were assigned in two groups: continuous half-dose GnRH agonist long protocol (Group A, n=63) vs. further reduced dose GnRH agonist long protocol (Group B, n=39) from half-dose at the start of GnRH agonist to 1/3 or 1/4 dose after pituitary suppression. Exogenous FSH or hMG was administered for COH in step-down mode, 4 or less embryos were transferred, and intramuscular progesterone or 8% progesterone gel was used for the luteal support. RESULTS: Serum estradiol (E2) level on hCG day was significantly higher in Group B (1,318.3 +/- 1,120.4 vs. 2,054.9 +/- 1,773.5 pg/mL, p=0.015). The number of transferable embryos was also significantly higher in Group B (2.9 +/- 1.7 vs. 3.7 +/- 2.0, p=0.027). There was no statistically significant difference in the outcomes such as the dose of gonadotropins administered, the number of oocytes retrieved, and the clinical pregnancy rate. CONCLUSION: GnRH agonist long protocol with the reduced dose from half-dose at the start to 1/3 or 1/4 of dose after pituitary suppression may be more beneficial for COH in IVF-ET patients with high basal serum FSH level. Further prospective randomized controlled study in a larger scale will be necessary to confirm this findings.

Clinical Efficacy of Reduced Dose GnRH Agonist Long Protocol for Controlled Ovarian Hyperstimulation in IVF-ET Patients with High Basal Serum FSH Level / 대한산부인과학회잡지

OBJECTIVE: To evaluate the clinical efficacy of half-dose and further reduced dose GnRH agonist long protocols for controlled ovarian hyperstimulation (COH) in in vitro fertilization and embryo transfer (IVF-ET) patients with high basal serum FSH level. METHODS: One hundred and two IVF-ET cycles performed in 84 infertile patients with high basal serum FSH level (FSH>10.0 mIU/mL) were included in this retrospective study. Study subjects were assigned in two groups: continuous half-dose GnRH agonist long protocol (Group A, n=63) vs. further reduced dose GnRH agonist long protocol (Group B, n=39) from half-dose at the start of GnRH agonist to 1/3 or 1/4 dose after pituitary suppression. Exogenous FSH or hMG was administered for COH in step-down mode, 4 or less embryos were transferred, and intramuscular progesterone or 8% progesterone gel was used for the luteal support. RESULTS: Serum estradiol (E2) level on hCG day was significantly higher in Group B (1,318.3 +/- 1,120.4 vs. 2,054.9 +/- 1,773.5 pg/mL, p=0.015). The number of transferable embryos was also significantly higher in Group B (2.9 +/- 1.7 vs. 3.7 +/- 2.0, p=0.027). There was no statistically significant difference in the outcomes such as the dose of gonadotropins administered, the number of oocytes retrieved, and the clinical pregnancy rate. CONCLUSION: GnRH agonist long protocol with the reduced dose from half-dose at the start to 1/3 or 1/4 of dose after pituitary suppression may be more beneficial for COH in IVF-ET patients with high basal serum FSH level. Further prospective randomized controlled study in a larger scale will be necessary to confirm this findings.