Early and late relapses of multiple myeloma after autologous haematopoietic stem cell transplantation

Introduction. Autologous haematopoietic stem cell transplantation (auto-HSCT) is a highly effective treatment for multiple myeloma (MM). Auto-HSCT allows a signifi cant improvement of haematological response leading to higher overall survival and quality of life in MM patients. Nonetheless, the majority of patients develop relapse.Aim — a comparison of clinical MM relapses developing at variant terms after auto-HSCT.Patients and methods. A retrospective study enrolled 65 MM patients aged between 39 and 64 years. All patients had auto-HSCT during 2009–2019, all had achieved complete response (CR) or very good partial response (VGPR) and all since developed immunochemical MM relapse in laboratory evidence. Patients were divided in two cohorts by relapse term, the early (within 12 months of auto-HSCT) and late relapse.Results. Early immunochemical relapse was diagnosed in 13 (20 %), late relapse — in 52 (80 %) patients. The dependence between relapse term and depth of post-auto-HSCT antitumour response has been determined. The proportion of CR patients was signifi cantly higher in late than in early relapse (55.8 vs. 23 %). In follow-up, 60 patients (92.3 %) were initiated on antirelapse therapy, all early relapse and 90.3 % late relapse patients. On day +100 of auto-HSCT, CR patients had later relapse vs. VGPR individuals (median 24 vs. 19.9 months, p = 0.08) with signifi cantly weaker paraprotein secretion resembling the clinical course of monoclonal gammopathy of unclear signifi cance (MGUS).Conclusion. Auto-HSCT allows long-term control of the disease. A signifi cant prognostic factor is antitumour response on +100 day of auto-HSCT. Patients attaining CR have later relapse progressing in a MGUS-like manner. Patients with late indolent relapse can be managed long-term without antitumour therapy.

Whole-body magnetic resonance imaging for diagnosis and treatment monitoring in multiple myeloma

Introduction. Whole-body diffusion-weighted magnetic resonance imaging (MRI) is an informative method for bone marrow infiltration diagnosis in patients with multiple myeloma (MM) and post-monitoring in autologous haematopoietic stem cell transplantation (auto-HSCT).Aim: to study bone marrow lesions in MM patients using whole-body MRI prior to and after chemotherapy with subsequent auto-HSCT.Materials and methods. Forty patients with MM were included in a prospective study of whole-body MRI before and after high-dose chemotherapy with auto-HSCT. All patients had whole-body MRI prior to and at +100 day of auto-HSCT. Antitumour response was assessed after induction and at +100 day. The number and volume of bone marrow lesions prior to and at +100 day of auto-HSCT were determined, along with apparent diffusion coefficient (ADC) in the lesions.Results. We observed a significant reduction of 29 % in the number of lesions, 40 % — in their volume and 33 % — in ADC. A significant correlation was revealed between relative reduction in the number and volume of foci (r = 0.52, p = 0.0017). A correlation was found between relative reduction in the foci number and ADC (r = 0.47, p = 0.016). Patients with lesions > 7 cm3 in MRI data exhibited a lesser reduction in the foci number and volume and ADC values after auto-HSCT compared to patients with lesions < 7 cm3.Conclusion. Whole-body MRI with diffusion-weighted imaging and subsequent estimation of the number and volume of lesions and their ADC values prior to and after auto-HSCT add power to assessing antitumour response in MM patients with auto-HSCT.

Desired Turbulence? Gut-Lung Axis, Immunity, and Lung Cancer

The microbiota includes different microorganisms consisting of bacteria, fungi, viruses, and protozoa distributed over many human body surfaces including the skin, vagina, gut, and airways, with the highest density found in the intestine. The gut microbiota strongly influences our metabolic, endocrine, and immune systems, as well as both the peripheral and central nervous systems. Recently, a dialogue between the gut and lung microbiota has been discovered, suggesting that changes in one compartment could impact the other compartment, whether in relation to microbial composition or function. Further, this bidirectional axis is evidenced in an, either beneficial or malignant, altered immune response in one compartment following changes in the other compartment. Stimulation of the immune system arises from the microbial cells themselves, but also from their metabolites. It can be either direct or mediated by stimulated immune cells in one site impacting the other site. Additionally, this interaction may lead to immunological boost, assisting the innate immune system in its antitumour response. Thus, this review offers an insight into the composition of these sites, the gut and the lung, their role in shaping the immune system, and, finally, their role in the response to lung cancer.

Improving TCR Gene Therapy for Treatment of Haematological Malignancies

Adoptive immunotherapy using TCR gene modified T cells may allow separation of beneficial Graft versus tumour responses from harmful GvHD. Improvements to this include methods to generate high avidity or high affinity TCR, improvements in vector design and reduction in mispairing. Following adoptive transfer, TCR transduced T cells must be able to survive and persist in vivo to give most effective antitumour responses. Central memory or naive T cells have both been shown to be more effective than effector cells at expanding and persisting in vivo. Lymphodepletion may enhance persistence of transferred T cell populations. TCR gene transfer can be used to redirect CD4 helper T cells, and these could be used in combination with CD8+ tumour specific T cells to provide help for the antitumour response. Antigen specific T regulatory T cells can also be generated by TCR gene transfer and could be used to suppress unwanted alloresponses.