Summary
A joint working group established by the Haemato‐oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Society for Bone Marrow Transplantation (BSBMT) ...has reviewed the available literature and made recommendations for the diagnosis and management of acute graft‐versus‐host disease. This guideline includes recommendations for the diagnosis and grading of acute graft‐versus‐host disease as well as primary treatment and options for patients with steroid‐refractory disease. The goal of treatment should be effective control of graft‐versus‐host disease while minimizing risk of toxicity and relapse.
Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells ...were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMφs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMφs to populate the niche and that the presence of beMφs does not alter behavior. Furthermore, beMφs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMφs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMφs may be possible with irradiation-free conditioning regimens.
Several reports have suggested that mesenchymal stem cells (MSCs) could exert a potent immunosuppressive effect in vitro, and thus may have a therapeutic potential for T cell-dependent pathologies. ...We aimed to establish whether MSCs could be used to control graft-vs-host disease (GVHD), a major cause of morbidity and mortality after allogeneic hemopoietic stem cell transplantation. From C57BL/6 and BALB/c mouse bone marrow cells, we purified and expanded MSCs characterized by the lack of expression of CD45 and CD11b molecules, their typical spindle-shaped morphology, together with their ability to differentiate into osteogenic, chondrogenic, and adipogenic cells. These MSCs suppressed alloantigen-induced T cell proliferation in vitro in a dose-dependent manner, independently of their MHC haplotype. However, when MSCs were added to a bone marrow transplant at a MSCs:T cells ratio that provided a strong inhibition of the allogeneic responses in vitro, they yielded no clinical benefit on the incidence or severity of GVHD. The absence of clinical effect was not due to MSC rejection because they still could be detected in grafted animals, but rather to an absence of suppressive effect on donor T cell division in vivo. Thus, in these murine models, experimental data do not support a significant immunosuppressive effect of MSCs in vivo for the treatment of GVHD.
Tissue-resident macrophages can originate from embryonic or adult hematopoiesis. They play important roles in a wide range of biological processes including tissue remodeling during organogenesis, ...organ homeostasis, repair following injury, and immune response to pathogens. Although the origins and tissue-specific functions of resident macrophages have been extensively studied in many other tissues, they are not well characterized in skeletal muscle. In the present study, we have characterized the ontogeny of skeletal muscle-resident macrophages by lineage tracing and bone marrow transplant experiments. We demonstrate that skeletal muscle-resident macrophages originate from both embryonic hematopoietic progenitors located within the yolk sac and fetal liver as well as definitive hematopoietic stem cells located within the bone marrow of adultmice. Single-cell-based transcriptome analyses revealed that skeletal muscle-resident macrophages are distinctive from resident macrophages in other tissues as they express a distinct complement of transcription factors and are composed of functionally diverse subsets correlating to their origins. Functionally, skeletal muscleresident macrophages appear to maintain tissue homeostasis and promote muscle growth and regeneration.
The role of the vascularized bone marrow component as a continuous source of donor-derived hematopoietic stem cells that facilitate tolerance induction of vascularized composite allografts is not ...completely understood. In this study, vascularized composite tissue allograft transplantation outcomes between recipients receiving either conventional bone marrow transplantation (CBMT) or vascularized bone marrow (VBM) transplantation from Balb/c (H2d) to C57BL/6 (H2b) mice were compared. Either high- or low-dose CBMT (1.5 × 10
or 3 × 10
bone marrow cells, respectively) was applied. In addition, recipients were treated with costimulation blockade (1 mg anti-CD154 and 0.5 mg CTLA4Ig on postoperative days 0 and 2, respectively) and short-term rapamycin (3 mg/kg/day for the first posttransplant week and then every other day for another 3 weeks). Similar to high-dose conventional bone marrow transplantation, 5/6 animals in the vascularized bone marrow group demonstrated long-term allograft survival (>120 days). In contrast, significantly shorter median survival was noted in the low-dose CBMT group (~64 days). Consistently high chimerism levels were observed in the VBM transplantation group. Notably, low levels of circulating CD4
and CD8
T cells and a higher ratio of Treg to Teff cells were maintained in VBM transplantation and high-dose CBMT recipients (>30 days) but not in low-dose VBM transplant recipients. Donor-specific hyporesponsiveness was shown in tolerant recipients in vitro. Removal of the vascularized bone marrow component after secondary donor-specific skin transplantation did not affect either primary allograft or secondary skin graft survival.
Purpose
The US does not have universal paid family and medical leave. We examine the direct effects of access to paid leave on patient-reported health, quality of life (QOL), and perceived stress of ...employed patients who underwent bone marrow transplantation (BMT) to treat advanced blood cancer as well as the indirect effects through reductions in the financial burden (FB) that patients face.
Methods
Our cross-sectional observational study took place at three US transplantation centers in 2014 and 2015. All English-speaking cancer patients 6-month post-BMT were mailed a 43-item survey assessing financial situation, employer benefits, and patient-reported health outcomes. The sample includes the 171 respondents who were employed at the time of BMT.
Results
Seemingly unrelated regression analysis confirms that patient access to paid leave was associated with reductions in all three measures of FB, and lower levels of financial hardship were related with improved health, QOL, and perceived stress outcomes. For self-reported health and perceived stress outcomes, all of the effects of patient paid leave operate indirectly through reductions in FB. For QOL outcomes, there is both a direct effect (over 80%) of paid leave and an indirect effect through reduction of FB.
Conclusion
We found that paid leave affected health outcomes for BMT patients mostly through alleviating FB. These findings suggest universal paid leave policies in the US might alleviate financial hardship and have positive effects on the self-reported QOL of employed patients facing intensive medical treatments.
Background: The parametric g-formula can be used to estimate the effect of a policy, intervention, or treatment. Unlike standard regression approaches, the parametric g-formula can be used to adjust ...for time-varying confounders that are affected by prior exposures. To date, there are few published examples in which the method has been applied. Methods: We provide a simple introduction to the parametric g-formula and illustrate its application in an analysis of a small cohort study of bone marrow transplant patients in which the effect of treatment on mortality is subject to time-varying confounding. Results: Standard regression adjustment yields a biased estimate of the effect of treatment on mortality relative to the estimate obtained by the g-formula. Conclusions: The g-formula allows estimation of a relevant parameter for public health officials: the change in the hazard of mortality under a hypothetical intervention, such as reduction of exposure to a harmful agent or introduction of a beneficial new treatment. We present a simple approach to implement the parametric g-formula that is sufficiently general to allow easy adaptation to many settings of public health relevance.
Cancer treatment during COVID-19 pandemic Jindal, Vishal; Sahu, Kamal Kant; Gaikazian, Susanna ...
Medical oncology (Northwood, London, England),
07/2020, Letnik:
37, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Currently world is fighting with global pandemic of coronavirus disease 2019 (COVID-19). At this time of uncertainty, oncologists are struggling to provide appropriate care to cancer patients. They ...have to weigh risk and benefit of giving cancer treatment vs chances of getting them infected with COVID-19. As cancer patients are immunocompromised and there are high chances of exposure during hospital visits and if they get infected, outcome can be fatal. So through the column of this article, we would like to provide basic guideline in management of cancer patients during COVID-19 pandemic.
We report the results from a multicenter retrospective study of 69 adult patients who underwent haploidentical blood or marrow transplantation (haplo-BMT) with post-transplantation cyclophosphamide ...(PTCy) for chronic phase myelofibrosis. The median age at BMT was 63 years (range, 41-74). Conditioning regimens were reduced intensity in 54% and nonmyeloablative in 39%. Peripheral blood grafts were used in 86%. The median follow-up was 23.1 months (range, 1.6-75.7). At 3 years, the overall survival, relapse-free survival (RFS), and graft-versus-host-disease (GVHD)-free-RFS were 72% (95% CI 59-81), 44% (95% CI 29-59), and 30% (95% CI 17-43). Cumulative incidences of non-relapse mortality and relapse were 23% (95% CI 14-34) and 31% (95% CI 17-47) at 3 years. Spleen size ≥22 cm or prior splenectomy (HR 6.37, 95% CI 2.02-20.1, P = 0.002), and bone marrow grafts (HR 4.92, 95% CI 1.68-14.4, P = 0.004) were associated with increased incidence of relapse. Cumulative incidence of acute GVHD grade 3-4 was 10% at 3 months and extensive chronic GVHD was 8%. Neutrophil engraftment was reported in 94% patients, at a median of 20 days (range, 14-70). In conclusion, haplo-BMT with PTCy is feasible in patients with myelofibrosis. Splenomegaly ≥22 cm and bone marrow grafts were associated with a higher incidence of relapse in this study.
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