Intensifying Methotrexate (MTX) Dosage Reduces Treatment Failure in Adults with Burkitt or Burkitt-Like Leukaemia/Lymphoma (BL) Treated with an Adapted BFM Protocol.

Abstract The use of short-duration intensive combination chemotherapy protocols has improved survival in adults with Burkitt/Burkitt-like leukaemia and lymphoma (BL). Systemic methotrexate (MTX) is an integral component of these regimens, but the dosage varies between treatment schedules, and the precise dose required to optimise tumour-kill without causing severe toxicity is not known. In this study of 66 adults with sporadic BL, we have investigated whether the dosing intensity of MTX can influence treatment failure (defined as disease relapse or resistance to treatment, or death due to therapy). There were 49 males and 17 females in the cohort (median age 36 years, range 16–69y), including 9 with HIV disease and 2 organ-transplant recipients. Majority of patients (66%) had St Jude stage III/IV disease. The median increase in serum LDH level relative to normal (adjusted LDH) was 1.4 (range 1–65). Patients were treated with a combination of CNS-directed and systemic chemotherapy comprising of a pre-phase [fractionated (Fr) cyclophosphamide and prednisolone], followed by a possible total of 6 cycles of alternating Fr ifosfamide, dexamethasone, vincristine, cytarabine and etoposide [Cycle A], with Fr cyclophosphamide, dexamethasone, vincristine and adriamycin [Cycle B] as outlined by the German BFM paediatric protocols. Patients received a 24h intravenous infusion of MTX on d1 of each cycle of treatment. Based on the mean MTX dose administered per cycle, patients were stratified into three dosage groups: low (<1gm/m2, n=4), intermediate (1–1.5g/m2, n=24) or high (>1.5–3g/m2, n=34). There were 3 toxic deaths, disease was refractory in 8 patients and 9 experienced disease relapse. Durable complete responses following BFM were observed in 46/66 (70%) patients. A significantly lower proportion of patients receiving high-dose MTX (17%) experienced treatment failure compared to 45% and 50% in the intermediate and low-dose groups respectively (Fisher’s Exact p=0.01). Risk stratification on the basis of pre-treatment stage and bulk of disease, adjusted LDH and ECOG score was however unable to identify patients who may benefit from intensifying MTX dosage. These data thus uniquely highlight the impact of MTX dose in influencing outcomes in adult BL as well as the need for novel biological markers to identify patients requiring additional therapeutic strategies.

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Faculty Opinions recommendation of A Double-Blind, Randomized Trial of High-Dose vs Standard-Dose Influenza Vaccine in Adult Solid-Organ Transplant Recipients.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732320399.793545911 ◽

2018 ◽

Author(s):

Olivier Lortholary

Keyword(s):

Influenza Vaccine ◽

Randomized Trial ◽

Standard Dose ◽

Organ Transplant ◽

Solid Organ Transplant ◽

High Dose ◽

Solid Organ ◽

Transplant Recipients ◽

Double Blind ◽

Solid Organ Transplant Recipients

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The underrepresentation of female participants in studies assessing the impact of high-dose exercise on cardiovascular outcomes: a scoping review

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.367 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

S Pallikadavath ◽

R Patel ◽

CL Kemp ◽

M Hafejee ◽

N Peckham ◽

...

Keyword(s):

Scoping Review ◽

High Volume ◽

Cardiovascular Outcomes ◽

High Dose ◽

Funding Sources ◽

Review Protocol ◽

The Mean ◽

The Impact ◽

Over Time ◽

Funding Acknowledgements

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiovascular adaptations as a result of exercise conducted at high-intensity and high-volume are often termed the ‘Athlete’s heart’. Studies have shown that these cardiovascular adaptations vary between sexes. It is important that both sexes are well represented in this literature. However, many studies assessing the impact of high-dose exercise on cardiovascular outcomes under-recruit female participants. Purpose This scoping review aimed to evaluate the representation of females in studies assessing the impact of high-dose exercise on cardiovascular outcomes and demonstrate how this has changed over time. Methods The scoping review protocol as outlined by Arksey and O’Malley was used. OVID and EMBASE databases were searched and studies independently reviewed by two reviewers. Studies must have investigated the effects of high-dose exercise on cardiovascular outcomes. To assess how the recruitment of females has changed over time, two methods were used. One, the median study date was used to categorise studies into two groups. Two, studies were divided into deciles to form ten equal groups over the study period. Mean percentage of female recruitment and percentage of studies that failed to include females were calculated. Results Overall, 250 studies were included. Over half the studies (50.8%, n = 127) did not include female participants. Only 3.2% (n = 8) did not include male participants. Overall, mean percentage recruitment was 18.2%. The mean percentage of recruitment was 14.5% before 2011 and 21.8% after 2011. The most recent decile of studies demonstrated the highest mean percentage of female recruitment (29.3%) and lowest number of studies that did not include female participants (26.9%). Conclusion Female participants are significantly underrepresented in studies assessing cardiovascular outcomes caused by high-dose exercise. The most recent studies show that female recruitment may be improving, however, this still falls significantly short for equal representation. Risk factors, progression and management of cardiovascular diseases vary between sexes, hence, translating findings from male dominated data is not appropriate. Future investigators should aim to establish barriers and strategies to optimise fair recruitment. Mean percentage females recruited per study (%) Percentage studies that do not include women (%) Overall (n = 250) 18.2 50.8 (n = 127) Studies before 2011 (n = 121) 14.5 59.5 (n = 72) Studies after 2011 (n = 129) 21.8 42.6 (n = 55) Table 1: Female recruitment characteristics. The year 2011 (median study year) was chosen as this divides all included studies into two equal groups.

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High-Dose Acyclovir for Cytomegalovirus Prophylaxis in Seropositive Abdominal Transplant Recipients

Annals of Pharmacotherapy ◽

10.1177/1060028017728296 ◽

2017 ◽

Vol 52 (1) ◽

pp. 5-10 ◽

Cited By ~ 5

Author(s):

Margaret R. Jorgenson ◽

Jillian L. Descourouez ◽

Glen E. Leverson ◽

Erin K. McCreary ◽

Michael R. Lucey ◽

...

Keyword(s):

Organ Transplant ◽

Invasive Disease ◽

High Dose ◽

Solid Organ ◽

Transplant Recipients ◽

Composite Failure ◽

Significant Difference ◽

Low Incidence ◽

Ganciclovir Resistance ◽

Long Term Impact

Background: Following abdominal solid organ transplant (aSOT), valganciclovir (VGC) is recommended for cytomegalovirus (CMV) prophylaxis. This agent is associated with efficacy concerns, toxicity, and emergence of ganciclovir resistance. Objective: To evaluate the incidence of high-dose acyclovir (HD-A) prophylaxis failure in seropositive aSOT recipients (R+). Methods: This was a retrospective, single-center study of R+ transplanted without lymphocyte-depleting induction between January 1, 2000, and June 30, 2013, discharged with 3 months of HD-A prophylaxis (800 mg 4 times daily). The primary outcome was incidence of prophylaxis failure. Secondary outcomes were incidence of biopsy-proven tissue-invasive disease and prophylaxis failure for each allograft subgroup. Results: A total of 1525 patients met inclusion criteria: 944 renal (RTX), 108 simultaneous pancreas-kidneys (SPK), 462 liver (LTX), and 11 pancreas (PTX) transplant recipients. The composite rate of HD-A prophylaxis failure was 7%; incidence of tissue-invasive disease was 0.4%. Failure rates were 4.5%, 6.1%, 11%, and 20% in the RTX, SPK, LTX, and PTX populations, respectively; tissue-invasive disease rates were 0.2%, 0%, 0.7%, and 10%. Failure occurred more frequently in the LTX and PTX populations ( P < 0.0001, HR = 2.6; P = 0.04 HR = 4.4). Incidence of tissue-invasive disease was minimal and not different in the RTX, LTX and SPK populations ( P = 0.34). When evaluating recipients of seronegative allografts (D−), the composite failure rate was 3.4% with no significant difference between allograft subgroups ( P = 0.45). Conclusion: HD-A may be a reasonable prophylaxis alternative for D−/R+ recipients, in the absence of lymphocyte-depleting induction, if low incidence viremia is tolerable. Future studies are needed to determine the long-term impact of CMV viremia in the setting of this prophylaxis approach.

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