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Problem definition: Treating many blood-related diseases requires transplantation of genetically compatible hematopoietic stem cells (HSCs) extracted from the bone marrow (BM) of live donors or the umbilical cord blood (CB) of babies. To facilitate the search for HSCs, institutions known as BM registries collect the details of potential donors and CB banks store units of CB. This paper focuses on the problem of joint optimization of the capacity of these two institutions. Academic/practical relevance: With more than 10 million genetic variants, limited inventory relative to this variety, and random replenishment, BM registry and CB bank compositions are random, interdependent, and change nondeterministically over time. Furthermore, BM and CB differ in their supply, costs, genetic matching criteria, and influences on medical outcomes, giving rise to important tradeoffs such that neither is preferred exclusively to the other. Jointly determining the optimal capacity of both sources is therefore both technically challenging and has immediate policy implications. Methodology: We develop a simulation-based approach to estimate the temporal variation in matching probabilities before incorporating the associated regression parameters into a mathematical model closely matching the research context. Results are contrasted against a simplified mathematical model, highlighting the importance of the dynamic setup. Results: Inventories of 17.5 million registered BM donors and 335,000 CB units are estimated as optimal for the U.S. population under reasonable assumptions. Expanding capacity to these levels would satisfy 33% of the currently unmet demand, increasing the transplantation rate to 98.7% and delivering $770 million of extra social surplus annually. Managerial implications: Rigorous policy analyses are imperative for designing evidence-based, cost-effective policies that deliver societal benefits. To this end, we provide quantitative evidence in support of calls for further expansion of the national BM registry and CB banks in the United States. We also propose annual recruitment targets for BM donors and CB units to maintain the two institutions at their suggested levels. History: This paper has been accepted for the Manufacturing & Service Operations Management Special Section on Responsible Research in Operations Management. Supplemental Material: The e-companion is available at https://doi.org/10.1287/msom.2022.1093. [ABSTRACT FROM AUTHOR]

Despite diagnostic advances, breast cancer remains the most prevalent cancer among women in the United States. The armamentarium of treatment options for metastatic disease is limited and mostly ineffective with regards to eradicating cancer. However, there have been novel findings in the recent literature that substantiate the function of the microenvironment in breast cancer progression and the support of metastasis to tertiary sites such as bone marrow. The uncovered significance of the microenvironment in the pathophysiology of breast cancer metastasis has served to challenge previously widespread theories and introduce new perspectives for the future research to eradicate breast cancer. This paper delineates the current understanding of the molecular mechanisms involved in the interactions between breast cancer cells and the microenvironment in progression, metastasis, and dormancy. The information, in addition to other mechanisms described in bone marrow, is discussed in the paper. [ABSTRACT FROM AUTHOR]

The article discusses the dynamics of what had actually happened in the U.S. with bone marrow transplants in breast cancer. More than 20,000 U.S. women had endured this treatment for no compelling reason. Many died because of it, while others were left with serious and long-lasting side effects.

Simple Summary: Cytokine release syndrome is a potentially life-threatening complication of therapy with T-cell engaging bispecific antibodies. Here we evaluated the risk, characteristics and biomarkers of treatment-emergent cytokine release syndrome in patients with relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome who received weekly intravenous infusions of the CD3xCD123 bispecific antibody APVO436. Cytokine release syndrome was encountered in 10 of 46 patients (21.7%) treated with APVO436 with a cumulative Grade 3/4 cytokine release syndrome incidence of 8.7%. Cytokine profiling in patients who developed cytokine release syndrome after APVO436 infusion indicated that the predominant cytokine in this inflammatory cytokine response was IL-6. The findings from this research provide new insights regarding the biology and effective management of cytokine release syndrome in leukemia patients treated with T-cell redirecting bispecific antibodies. We evaluate the risk, characteristics and biomarkers of treatment-emergent cytokine release syndrome (CRS) in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who received APVO436 during the dose-escalation phase of a Phase 1B study (ClinicalTrials.gov, identifier: NCT03647800). Of four patients who developed Grade ≥ 3 CRS, two received steroid prophylaxis. The dose level, gender, race, obesity, or baseline hematologic parameters in peripheral blood did not predict the risk of CRS. Patients with a higher leukemia burden as determined by a higher total WBC, higher percentage of blasts in bone marrow, or higher percentage of blasts in peripheral blood (by hematopathology or immunophenotyping) did not have a higher incidence of CRS. There was an age difference between patients who did versus patients who did not develop CRS (72.9 ± 1.6 years (Median 73.5 years) vs. 63.3 ± 2.3 years (Median: 65.0 years), which was borderline significant (p = 0.04). Premedication with steroids did not eliminate the risk of CRS. Cytokine profiling in patients who developed CRS after APVO436 infusion indicates that the predominant cytokine in this inflammatory cytokine response was IL-6. APVO436-associated CRS was generally manageable with tocilizumab with or without dexamethasone. Notably, the development of CRS after APVO436 therapy did not appear to be associated with a response. The prolonged stabilization of disease, partial remissions and complete remissions were achieved in both patients who experienced CRS, as well as patients who did not experience CRS after APVO436 infusions. [ABSTRACT FROM AUTHOR]

Background: Glyphosate is the most widely used herbicide in the USA and worldwide. There has been considerable debate about its carcinogenicity. Epidemiological studies suggest that multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) have a positive and statistically significant association with glyphosate exposure. As a B cell genome mutator, activation-induced cytidine deaminase (AID) is a key pathogenic player in both MM and B cell NHL. Methods: Vk*MYC is a mouse line with sporadic MYC activation in germinal center B cells and considered as the best available MM animal model. We treated Vk*MYC mice and wild-type mice with drinking water containing 1000 mg/L of glyphosate and examined animals after 72 weeks. Results: Vk*MYC mice under glyphosate exposure developed progressive hematological abnormalities and plasma cell neoplasms such as splenomegaly, anemia, and high serum IgG. Moreover, glyphosate caused multiple organ dysfunction, including lytic bone lesions and renal damage in Vk*MYC mice. Glyphosate-treated wild-type mice developed benign monoclonal gammopathy with increased serum IgG, anemia, and plasma cell presence in the spleen and bone marrow. Finally, glyphosate upregulated AID in the spleen and bone marrow of both wild-type and Vk*MYC mice. Conclusions: These data support glyphosate as an environmental risk factor for MM and potentially NHL and implicate a mechanism underlying the B cell-specificity of glyphosate-induced carcinogenesis observed epidemiologically. [ABSTRACT FROM AUTHOR]