Blood Stem Cell Transplantation Research Articles

Transplantation/cellular therapy in acute myeloid leukemia - Who, When, Why and How?

To date allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective immunotherapeutic approach for the treatment of acute myeloid leukemia (AML). It involves the transplantation of blood stem cells from a healthy donor into a patient, with the goal of using the donor's immune system to recognize and attack cancer cells (Graft-versus-leukemia effect). Thereby, allo-HSCT is more efficient than chemotherapy alone, as it combines high dose chemotherapy +/- irradiation with immunotherapy establishing a long-term control of leukemic cells while allowing reconstitution of a healthy donor hematopoiesis and a new immune system. However, the procedure carries significant risks, including the possibility of graft-versus-host disease (GvHD), and requires careful patient selection to ensure the best possible outcome. In AML patients with high-risk, relapsed or chemo-refractory disease allo-HSCT provides the only curative option.While allo-HSCT is currently the most established form of immunotherapy in the treatment of AML, other approaches that use the immune system to fight cancer are being researched. These may include immunomodulatory drugs or cell therapies such as CAR-T cells, which stimulate the immune system to attack cancer cells. Even if this does not yet play a role in current standard therapy, as our understanding of the immune system and its role in cancer grows, it is likely that targeted immunotherapies will become increasingly important in the treatment of AML The following article gives you an overview of allo-HSCT in AML patients and the current developments.

Clinical analysis of 76 patients with severe aplastic anemia treated with haploid hematopoietic stem cell transplantation

Objective: The purpose of this study is to determine the efficacy of haploidentical donor hematopoietic stem cell transplantation in the treatment of severe aplastic anemia. Methods: The clinical data of 76 patients with severe aplastic anemia (SAA) patients who underwent haplo-HSCT from December 2014 to October 2020 were selectively analyzed. There were 50 males and 26 females with a median age of 16 (3-52) years old. There were 49 SAA-Ⅰ patients, 18 SAA-Ⅱ patients, and 9 patients with hepatitis-associated aplastic anemia. There were 15 cases of bone marrow put together with peripheral blood stem cell transplantation and 61 cases of peripheral blood stem-cell transplantation. Conditioning regimens were Cyclophosphamide (CY) + Fludarabine (Flu) + ATG for 46 patients and Busulfan (Bu) + CY+Flu+ATG for 30 patients. Results: Three patients died during the myelosuppressive phase following transplantation, and 73 patients had a median time of neutrophil engraftment of 12 (9-21) days; in addition to 3 patients who died early, 8 patients did not obtain platelet reconstruction after transplantation, and 65 patients had platelet engraftment with a medium time of 14 (9-90) d. The incidence of primary graft failure was 10.9% and the incidence of secondary graft failure was 5.5%. The incidence of Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) was 38.4%, the incidence of Ⅲ-Ⅳ aGVHD was 16.4%, the incidence of chronic graft anti-host disease (cGVHD) was 35.8%, and the incidence of extensive cGVHD was 22.4%. The medium follow-up time was 19.5 (1-75) months, the prospective overall survival (OS) for 2 years was (78.6±5.0) %, the failure-free survival (FFS) was (75.9±5.1) %, and the transplant-related mortality was (20.2±4.9) %. Multi-factor analysis revealed that the patient older than 35 years old, Ⅲ/Ⅳ aGVHD, HCT-CI≥3, the pre-transplant ferritin ≥1 500 μg/L, the number of neutrophils >1×10(9)/L at the time of onset were risk factors affecting OS (P=0.008, 0.008, 0.014, 0.004, 0.027) . Patients with graft failure had lower OS and FFS than other patients (P<0.001) . Conclusion: Haplo-HSCT is an effective method for treating SAA in children, adolescents, and young patients, and the occurrence of severe aGVHD and severe infection, as well as graft failure, are the main causes of survival rate. The prevention and treatment of severe aGVHD and infection are essential to improve efficacy.

Impact of Clinical Parameters and Induction Regimens on Peripheral Blood Stem-Cell Mobilization and Collection in Multiple Myeloma Patients

Introduction: High-dose chemotherapy (HDCT) followed by autologous blood stem-cell transplantation (ABSCT) remains the standard consolidation therapy for newly diagnosed eligible multiple myeloma (MM) patients. As a prerequisite, peripheral blood stem cells (PBSCs) must be mobilized and collected by leukapheresis (LP). Many factors can hamper PBSC mobilization/collection. Here, we provide a comprehensive multiparametric assessment of PBSC mobilization/collection outcome parameters in a large cohort. Methods: In total, 790 MM patients (471 [60%] male, 319 [40%] female) who underwent PBSC mobilization/collection during first-line treatment were included. Evaluated PBSC mobilization/collection outcome parameters included the prolongation of PBSC mobilization, plerixafor administration, number of LP sessions, and overall PBSC collection goal/result. Results: 741 (94%) patients received cyclophosphamide/adriamycin/dexamethasone (CAD) and granulocyte-colony-stimulating factor (G-CSF) mobilization. Plerixafor was administered in 80 (10%) patients. 489 (62%) patients started LP without delay. 530 (67%) patients reached the PBSC collection goal at the first LP session. The mean overall PBSC collection result was 10.3 (standard deviation [SD] 4.4) × 106 CD34+ cells/kg. In a multiparametric analysis, variables negatively associated with PBSC mobilization/collection outcomes were female gender, age >60 years, an advanced ISS stage, and local radiation pre-/during induction, but not remission status postinduction. Notably, the identified risk factors contributed differently to each PBSC mobilization/collection outcome parameter. In this context, compared to all other induction regimens, lenalidomide-based induction with/without antibodies negatively affected only the number of LP sessions required to reach the collection goal, but no other PBSC mobilization/collection outcome parameters. In contrast, the probability of reaching a high collection goal of ≥6 × 106 CD34+ cells/kg body weight was higher after lenalidomide-based induction compared to VCD/PAD or VAD – taking into account – that a higher G-SCF dosage was given in approximately one-third of patients receiving lenalidomide-based induction with/without antibodies. Conclusion: Considering the identified risk factors in the clinical setting can contribute to optimized PBSC mobilization/collection. Moreover, our study demonstrates the necessity for a differentiated evaluation of PBSC mobilization/collection outcome parameters.

Role of the teenage and young adult blood and marrow stem-cell transplant clinical nurse specialist.

This article explores the role of the teenage and young adult (TYA) blood and marrow stem-cell transplant clinical nurse specialist (CNS) from the author's perspective, and the challenges of developing a novel role. The article aims to provide insight into the role, and review the benefits of the CNS to patient care, thus highlighting the value of developing such a role within other stem-cell transplant centres in the UK.

Bayesian inference in a generalized log-logistic proportional hazards model for the analysis of competing risk data: An application to stem-cell transplanted patients data

Typically, the parametric proportional hazard (PH) model is used to examine data on mortality occurrences. Competing risks are prevalent in health information, making it difficult to manage time to event data in clinical investigations. A Bayesian framework is being developed for managing conflicting risk occurrences in clinical data. The objective of this study is to identify the variables that affect patients' odds of surviving peripheral blood stem-cell transplantation, a therapy option for life-threatening blood disorders. In addition, we want to implement a Bayesian model capable of analysing time-to-event data in the context of competing risk. In this research, we analyse failure reasons in the setting of competing risk models using the generalised log-logistic with right-censored scheme.We present competing risks models for censored survival data in the presence of explanatory variables, where each system contains more than one component in series. We assume that each component's survival time follows a generalized log-logistic distribution. We obtain Bayesian estimates of the component's lifetime distribution parameters and regression coefficients. We present a comprehensive Markov chain Monte Carlo (McMC) method to evaluate the estimators' convergence diagnostics. A real-survival data set dealing with stem-cell transplants demonstrated the model's flexibility and advantages.

Anticipation of Relapse and Acute Graft-Versus-Host Disease after Allogeneic Peripheral Blood Stem Cell Transplantation: The Fundamental Role of Antigen-Presenting (Dendritic) Cells.

BackgroundDendritic cells (DCs) are antigen-presenting cells. In humans two distinct lineages of DCs exist: DC1 and DC2. Efforts to explore the role of DCs in acute graft-versus-host disease (aGVHD) after allogeneic peripheral blood stem–cell transplantation (PBSCT) are gaining traction. However, further research is needed to identify particular lineages and their values in terms of developing an evidence-based aGVHD- or relapse-prevention strategy. We monitored DC counts and subsets in PBSC grafts while harvesting stem cells in recipients to elucidate their value in anticipating disease relapse or aGVHD.MethodsWe enrolled 29 participants. Using fluorescence-activated cell sorting, total counts/kg of CD34+, DCs, and DC subsets were analyzed in 29 PBSC-graft components using CMRF44, CD11c, and CD4 monoclonal antibodies (MoAbs).ResultsIn the 29 grafts, we detected a significant positive correlation (P<0.01) between DCs and both DC1 and DC2. Significantly higher counts (P<0.01) of DCs and DC1 in those who had developed aGVHD (nine cases) were also observed. Relapsed cases (two) were also associated with higher counts of DCs and DC2. A significant positive correlation (P<0.05), was recorded between DCs and DC1 counts and the day of myeloid engraftment, while this was not detected on the day of platelet engraftment. Myeloid engraftment transpired earlier in patients without aGVHD. Increased DC-graft numbers, particularly DC1 measured by CD11c Moabs, were associated with aGVHD. Recipients of higher numbers of CD4bright DCs had an increased risk of relapse after allogeneic PBSCT.ConclusionThis study analyzed DCs in PBSC grafts, using novel specific MoAbs and flow cytometry. Our data showed that higher donor DC1 counts were linked to the incidence of aGVHD and DC2 with relapse. We propose a fundamental role for DC-graft monitoring in anticipating aGVHD and disease relapse.

Clinical trial and translational research for cancer immunology in Asian countries: Understanding the new frontier.

e14510 Background: Among the major advances in cancer treatment is the progress in cancer immunotherapy; however, despite the strides, there is few information specific to the Asian population. It is unclear to what extent clinical trial and translational research in cancer immunology are conducted in Asian institutions. Methods: This questionnaire-based survey was conducted among researchers and healthcare professionals who are involved in cancer immunology research and therapeutics in Asia-Pacific countries. The study identified the involvement of respondents in various phases of clinical trials, and immunotherapy research. In addition, the current capabilities of the institutions to conduct translational research were surveyed. Results: We received a total of 122 responses from 20 Asia-Pacific countries. More than half (58%) of the responders are currently conducting clinical trials on cancer immunology with 25% having performed more than 10 Phase 3 trials in the last 3 years. In clinical trials and clinical practice, immune checkpoint inhibitors were performed in most countries (81.8% and 88.6%, respectively). Clinical trials and clinical practice of CAR-T and TCR-T were performed only in some countries (CAR-T; 22.7% and 15.9%, TCR-T; 2.3% and 0%, respectively). In the absence of novel therapeutics in their institution, 18% of the responders refer their patient to facilities that have ongoing clinical trials. Among the institutions that perform Hematopoietic stem cell transplant (55.1%), the most common type offered include autologous (81.3%) and allogenic (70.8%) peripheral blood stem-cell transplantation. About 51.7% of the respondents have institutions that can conduct early drug phase development studies with only 11.2% capable of utilizing their own immunotherapeutic agents. Less than half of the respondents (40.7%) belong to institutions that have conducted translational researches using patient-derived samples for the last three years. Furthermore, more than half of the respondent institutions have no personnel that is experienced to handle and/or run patient-derived fresh peripheral blood or fresh tumors. Collaboration among neighboring countries can allow send out of specimens to other institutions that have such capability, however, 56.9% of countries have regulations or restrictions in transporting lymphocytes or tumor tissues. Conclusions: Oncologists and researchers in Asia recognize the importance of cancer immunology researches for patients. There were institutional and inter-country differences particularly in the conduct of early phase clinical drug development and translational research.

Трансплантация гемопоэтических клеток периферической крови от гаплоидентичных и неродственных доноров при острых лейкозах у детей, подростков и молодых взрослых: анализ конкурентного риска

Трансплантация гемопоэтических клеток периферической крови от гаплоидентичных и неродственных доноров при острых лейкозах у детей, подростков и молодых взрослых: анализ конкурентного рискаPeripheral blood stem cell transplantation from haploidentical and unrelated versus related donors for acute leukemia in children, adolescents and young adults (CAYA): A competing risk analysis

Clinical update-multiple myeloma

Multiple myeloma (MM) is amalignancy of hematopoetic system and is associated with destruction of bone, suppressed bone marrow function and renal failure. It is characterized by strong proliferation of malignant plasma cells. Classic therapies contained an alkylating agent and aglucocorticoid. In the 1990s, treatments were supplemented with transplantation of peripheral blood stem cells. During the 2000s, new therapies emerged, combining an immunomodulator (thalidomide, lenalidomide or pomalidomide), aproteasome inhibitor (bortezomib, carfilzomib or ixazomib), and amonoclonal antibody against CD38. Currently, antibodies against BCMA (B-cell maturation antigen), bispecific antibodies, and CAR T‑cell (chimeric antigen receptor T cells) therapies are being investigated in clinical trials. Classic diagnostics were based on end-organ damage, e.g., bone destruction, and estimated tumor load. Since 2014, new criteria for an earlier start of therapy were introduced-concentration of antibody light chains in blood serum, bone marrow lesions and its infiltration by malignant plasma cells. These lesions (clusters of myeloma cells) can be detected by magnetic resonance imaging (MRI) or positron emission tomography/computed tomography (PET/CT). Both methods are also used to monitor therapy response. Traditional X‑ray imaging has been replaced by the more gentle, low-dose CT. The standard diagnostic process is extended by cytogenetic examination of bone marrow samples via imaging fluorescent in situ hybridization (iFiSH) to identify patients at high risk. While most MM patients could be treated only palliatively until the 1990s, the prognosis has continuously improved since then. Nowadays, MM can be classified as achronic disease.

Pattern of Bacterial Infections in Indian Bone Marrow Transplant Patients - Experience from Chennai India

Introduction:Bone marrow transplant, both Autograft and Allograft produces profound immune-suppression and breach of mucosal surfaces leading to many opportunistic infections. There is a difference between infection pattern in countries like India compared to western countries. The western literature is more bothered about reactivation of viral and fungal infections, whereas Indian bone marrow transplant physicians are worried about losing patient to refractory gram negative sepsis. In this study, we have tried to decode the pattern of bacterial infections in Indian transplant patients and tried to suggest an antibiotic stewardship for the same.Materials and methods:This retrospective study included all bone marrow transplants with Febrile neutropenia done at our hospital from September 2014 to July 2021. A total of 440 patients were included and their pattern of bacterial infections with culture sensitivity and response to antibiotics were noted.Results:36% of patients we included in the study were aged between 40 to 60 years and the age range was from 2 years to 72 years. 59% were autograft and among Allograft 36% were haplo-identical bone marrow transplant. Nearly half the patients presented with fever above 99.5 F and tachycardia as the presenting sign. The WBC count during first episode febrile neutropenia was less than 100cells/cumm in around 25% patients. Empirical antibiotics post culture samples were initiated within 10 min in 95% of patients. Cefoperazone Sulbactum and Amikacin were started empirically as first line in all.Culture positivity rate was 22.7% of which 60% were multi-drug resistant gram negative bacilli which were sensitive only to Colistin / Fosfomycin / Tigecycline. This 60% MDR GNB is very high which may be partially due to MDR bugs in normal intestinal flora of patients from this part of the world. The common Gram-negative bacteria are Pseudomonas, Escherichia coli and Klebsiella. This made us to change antibiotic stewardship policy to Colistin / Fosfomycin / Ceftazidime avibactum very early in course in case of second fever / Hypotension or tachycardia. Our transplant related mortality is around 3% in Allograft due to sepsis and 0% in autograft. The rate of gram positive bacteremia is only 2% and this makes us think of avoiding drugs like Teicoplanin / Glycopeptides in first line empirical therapy.Conclusion:This seven year study had shown 22.7% culture positivity rate in febrile neutropenia transplant patients of which 60% are multi-drug resistant bacteria which is highly contrary to western literature. The rate of gram positive culture growth is only 2% which is lower than western literature. This study implies the importance of region and center specific antibiotic policy for febrile neutropenia and a generalized policy may not work always.Reference:-1. Ghafur A, Devarajan V, Raj R, Easow J, Raja T. Spectrum of bacteremia in posthematopoietic stem cell transplant patients from an Indian center. Indian J Cancer 2016;53:590-12. Krüger W,et al. Early infections in patients undergoing bone marrow or blood stem cell transplantation–a 7 year single centre investigation of 409 cases. Bone Marrow Transplant. 1999 Mar;23(6):589-97. doi: 10.1038/sj.bmt.1701614. PMID: 10217190. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prophylactic Peripheral Blood Stem Cell Collection in Patients with Extensive Bone-Marrow Infiltration of Neuroendocrine Tumours Prior to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE.

Peptide receptor radionuclide therapy (PRRT) of metastatic neuroendocrine tumors (NET) can be successfully repeated but may eventually be dose-limited. Since 177Lu-DOTATATE dose limitation may come from hematological rather than renal function, hematological peripheral blood stem cell backup might be desirable. Here, we report our initial experience of peripheral blood stem-cell collection (PBSC) in patients with treatment-related cytopenia and therefore high risk of bone-marrow failure. Five patients with diffuse bone-marrow infiltration of NET and relevant myelosuppression (≥grade 2) received PBSC before one PRRT cycle with 177Lu-DOTATATE (7.6 ± 0.8 GBq/cycle). Standard stem-cell mobilization with Granulocyte-colony stimulating factor (G-CSF) was applied, and successful PBSC was defined as a collection of >2 × 106/kg CD34+ cells. In case of initial failure, Plerixafor was administered in addition to G-CSF prior to apheresis. PBSC was successfully performed in all patients with no adverse events. Median cumulative activity was 44.8 GBq (range, 21.3–62.4). Three patients had been previously treated with PRRT, two of which needed the addition of Plerixafor for stem-cell mobilization. Only one of five patients required autologous peripheral blood stem-cell transplantation during the median follow up time of 28 months. PBSC collection seems to be feasible in NET with bone-marrow involvement and might be worth considering as a backup strategy prior to PRRT, in order to overcome dose-limiting bone-marrow toxicity.

Hemoglobinuria in the Early Poststem-Cell-Transplant Period: Risk Factors and Association with Outcomes.

Information on risk factors of hemoglobinuria after hematopoietic stem-cell transplant (HSCT) and its association with AKI, mortality, and engraftment is limited. We conducted a retrospective cohort study on all consecutive adults that underwent HSCT from January 6, 1999, to November 6, 2017. The study included 6039 patients that underwent bone marrow transplantation (BMT), umbilical cord blood, and peripheral blood stem-cell transplantation (PBSCT). Early post-HSCT, AKI occurred in 393 (7%) patients, and 52 (0.9%) patients had post-HSCT hemoglobinuria. Post-HSCT hemoglobinuria was associated with graft type (BMT+Cord), underlying disease (lymphoma, acute leukemia), and fludarabine-based conditioning regimen. Post-HSCT hemoglobinuria was associated with early (48-72 hours) post-HSCT AKI. Graft type (BMT+Cord) was associated with AKI among patients with hemoglobinuria. AKI in patients with hemoglobinuria was associated with delayed platelet engraftment and delayed WBC engraftment but not 100-day mortality. Close monitoring is recommended in this patient group to facilitate a good engraftment outcome.

МИНИ-ФОТОФЕРЕЗ – ЭКСТРАКОРПОРАЛЬНЫЙ ФОТОФЕРЕЗ, НЕ ТРЕБУЮЩИЙ ЛЕЙКАФЕРЕЗА: ОПЫТ КЛИНИЧЕСКОГО ИСПОЛЬЗОВАНИЯ

Extracorporeal photopheresis (ECP) has proven effectiveness for treatment of several diseases, including acute and chronic graft-versus-host disease (GVHD) after allogenic transplantation of hematopoietic blood stem cells. The standard ECP requires leukapheresis to obtain a mononuclear cell fraction. The possibility of using leukapheresis is limited by the requirements for vascular access and the somatic status of the patient. There is a relatively new method of performing ECF, called «mini-photopheresis» (mini-ECF), in which a fraction of mononuclear cells is isolated from a dose of whole blood obtained by the exfusion method. The article presents preliminary results of using mini-ECP in patients with acute and chronic GVHD. Materials and methods of research: the study included 11 patients with acute (7 patients) and chronic (4 patients) GVHD who received mini-ECP therapy from June 2018 to January 2021. Leukocyte fractions rich in mononuclear cells were prepared from the dose of whole blood of patients. The resulting fraction was diluted with 0,9% NaCl solution to less than 3% hematocrit. The cellular product was then injected with an 8-Methoxyperalene and programmed with UV spectrum A. Autologous erythrocytes and the finished cellular product were injected into the patient after irradiation. Results: 6 out of 7 patients (85,7%) with acute GVHD has responded to mini-ECP therapy. In patients with chronic GVHD, the response rate to mini-ECP therapy was 25%. In both groups there are no significant differences found in the number of leukocytes count per body mass in the finished cellular product. The correlation between the presence and severity of response to mini-ECP therapy with the number of leukocytes in the finished cellular product was not determined. None of the patients had adverse reactions and complications associated with mini-ECP therapy. Conclusion: mini-ECP is an attractive alternative for treatment of patients with steroid-resistant or steroid-dependent GVHD who cannot undergo leukapheresis. Our results are preliminary, but promising. We will continue to use this method as a second-line therapy for patients with contraindications to leukapheresis.

Body image issues and self-concept dilemmas in adolescents living with thalassemia

ABSTRACT Thalassemia, a genetic blood disorder, involves an inability to produce sufficient hemoglobin and comprises two types: alpha thalassemia and beta thalassemia. Beta thalassemia’s immediate treatment measures include frequent blood transmissions, stem cell and bone marrow transplants; all capable of altering an individual’s idea of body image, self-concept, growth, and socialization, resulting in several emotional, psychological, and behavioral concerns. This study aimed at comprehending the dilemmas of body image and self-concept encountered by adolescents with thalassemia, particularly the resulting influence on physical development and socialization. Using the phenomenological interpretivism approach of qualitative research, data was collected using purposive-convenient sampling from 11 adolescents, both boys and girls ranging from ages 12 to 18, living with thalassemia and undergoing treatment. The research highlights adolescent concerns with body image, specifically with complexion, facial features, being either underweight or overweight, all amalgamating into a self-concept dilemma. Moreover, results point to the significant influence of experiences with family, peers, educational institutions, and hospital staff. Therapeutic attention, through regular screening and counselling, should be provided to adolescent thalassemia patients to address the psychological aspects of the chronic illness.

Can early treatment of twitcher mice with high dose AAVrh10-GALC eliminate the need for BMT?

Introduction: Krabbe disease (KD) is an autosomal recessive disorder caused by mutations in the galactocerebrosidase (GALC) gene resulting in neuro-inflammation and defective myelination in the central and peripheral nervous systems. Most infantile patients present with clinical features before six months of age and die before two years of age. The only treatment available for pre-symptomatic or mildly affected individuals is hematopoietic stem cell transplantation (HSCT). In the animal models, combining bone marrow transplantation (BMT) with gene therapy has shown the best results in disease outcome. In this study, we examine the outcome of gene therapy alone. Methods: Twitcher (twi) mice used in the study, have a W339X mutation in the GALC gene. Genotype identification of the mice was performed shortly after birth or post-natal day 1 (PND1), using polymerase chain reaction on the toe clips followed by restriction enzyme digestion and electrophoresis. Eight or nine-day-old affected mice were used for gene therapy treatment alone or combined with BMT. While iv injection of 4 × 1013 gc/kg of body weight of viral vector was used originally, different viral titers were also used without BMT to evaluate their outcomes. Results: When the standard viral dose was increased four- and ten-fold (4X and 10X) without BMT, the lifespans were increased significantly. Without BMT the affected mice were fertile, had the same weight and appearance as wild type mice and had normal strength and gait. The brains showed no staining for CD68, a marker for activated microglia/macrophages, and less astrogliosis than untreated twi mice. Conclusion: Our results demonstrate that, it may be possible to treat human KD patients with high dose AAVrh10 without blood stem cell transplantation which would eliminate the side effects of HSCT.

Морфологічний стан трофічних виразок венозної етіології після трансплантації стовбурових клітин кордової крові

The aim. The research deals with analysis of the degree of regenerative processes activity in patients with trophic venous ulcers of the lower extremities that do not heal for a long time on the background of cell transplantation of cord blood stem cells and without. The study involved 32 patients with long-term non-healing trophic venous ulcers of venous etiology. Results and discussion. The study results showed that the healing process of the main group patients began in the first days after transplantation to reduce pericellular edema and inflammatory hyperemia of the soft tissues around the ulcer. When examining the histological features of the central skin ulcers of patients in the control group on the fifth day after treatment, we found out that the bottom surface of the ulcers was covered with homogeneous masses of the type of fibrinoid necrosis. Ulcers had a variable depth, in some places reached the fiber, with sweat and sebaceous glands, hair follicles in the course of defects were completely destroyed, in these places there were hemorrhages and young granulation tissue. In patients of the main group, the surface of the bottom of the ulcer was covered with homogeneous masses of fibrinoid necrosis, but the masses of fibrinoid necrosis were visually expressed three times less than in the control group, but the most important was that they always alternated with "veins" consisting of cells type of lymphoid. Immunohistochemical analysis for Willebrand factor in patients of the main group revealed unevenly scattered small compact groups of positively stained cells, which should be evaluated as foci of neoplasms of blood vessels more evenly distributed among the blood vessels of granulation tissue, in contrast to the control group. On the 14th day of the clinical study at the bottom of the ulcer in the main group there were morphological signs of better maturation of granulation tissue, as seen by more uniform and intensive processes of collagen fiber formation (increase in specific volume of collagen fibers) and blood vessels (decrease in specific volume of blood vessels) and the maturation of lymphoid (polypotent) cells into fibroblasts with more complete production of vimentin in them and endothelial cells with more complete production of Willebrand factor in them. It should be noted that there was a more complete resorption of fibrinoid necrosis masses in the main observation group compared to the control group of patients, which should also contribute to faster and more complete healing of the ulcer

Relief of HHV-6 Encephalomyelitis-induced Electric Shock-like Pain with Levetiracetam after Blood Stem Cell Transplantation

Relief of HHV-6 Encephalomyelitis-induced Electric Shock-like Pain with Levetiracetam after Blood Stem Cell Transplantation

Quality of life of patients with chronic trophic ulcers of venous etiology

The quality of life of patients with trophic ulcers of venous etiology using the the Chronic Venous Insufficiency Questionnaire (CIVIQ) was studied. To assess the quality of life of the patient, the questionnaire was conducted before the transplantation of cord blood stem cells, 1 and 6 months after surgery. Patients in group I had a higher assessment of quality of life, because the healing process of the ulcer was faster, the feeling of pain decreased and as a result the patient's psycho-emotional state improved. In addition, the surveyed 12 (85.7%) surveyed patients of group I noted that even with the preservation of some symptoms, their subjective manifestations were reduced and the feeling has improved. All this helped to improve the assessment of the quality of life of patients with trophic ulcers of the lower extremities, which were treated according to our proposed method.

Progressive or relapsed Burkitt lymphoma or leukemia in children and adolescents after BFM-type first-line therapy

AbstractChildren with refractory or relapsed Burkitt lymphoma (BL) or Burkitt leukemia (B-AL) have a poor chance to survive. We describe characteristics, outcome, reinduction, and transplantation approaches and evaluate risk factors among children with progression of a BL/B-AL included in Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Münster studies between 1986 and 2016. Treatment recommendation was reinduction including rituximab from the early 2000s followed by blood stem cell transplantation. The 3-year survival of the 157 children was 18.5 ± 3%. Survival significantly improved from 11 ± 3% before to 27 ± 5% after 2000 (P < .001), allowing for risk factor analyses among the latter 75 patients. Survival of 14 patients with relapse after initial therapy for low-risk disease (R1/R2) was 50 ± 13% compared with 21 ± 5% for 61 patients progressing after R3/R4 therapy (P < .02). A total of 25 of 28 patients with progression during first-line therapy, 31 of 32 with progression during reinduction, 15 of 16 not reaching a complete remission (CR) before transplantation, 9 of 10 treated with rituximab front-line, and all 13 patients not receiving rituximab during reinduction died. Forty-six patients received stem cell transplantation (20 autologous, 26 allogeneic). Survival after a regimen combining rituximab with continuous-infusion chemotherapy followed by allogeneic transplantation was 67 ± 12% compared with 18 ± 5% for all other regimen and transplantations (P = .003). Patients with relapsed BL/B-AL have a poor chance to survive after current effective front-line therapies. Progression during initial or reinduction chemotherapy and initial high-risk disease are risk factors in relapse. Time-condensed continuous-infusion reinduction followed by stem cell transplantation forms the basis for testing new drugs.

Nonhepatosplenic γδ T-Cell Lymphoma: A Subset of Cytotoxic Lymphomas With Mucosal or Skin Localization

AbstractHuman γδ T lymphocytes represent a minor subset of T cells in the peripheral blood, which exhibit a limited diversity and a tissue-restricted repertoire in contrast to their broad specificity. Most postthymic neoplasms that arise from this T-cell subpopulation belong to the hepatosplenic γδ lymphoma entity. Only a few cases of nonhepatosplenic γδ lymphomas have been described in detail previously. This study presents the clinicopathologic features of 11 consecutive cases of nonhepatosplenic γδ lymphoma. All were characterized by mucosal or skin initial involvement: nasal cavity (n = 3), gastrointestinal tract (n = 3), skin (n = 3), lung (n = 1), larynx (n = 1). Most patients presented with B symptoms (eight of 11), without peripheral lymphadenopathy and bone marrow involvement. A past history of chronic antigen exposure was noted in six cases, and four patients had features of immune deficiency. On histology, they were classified as pleomorphic tumors. Features of epitheliotropism and angiocentrism was observed in most cases. Tumor cells had a CD2+, CD3+, T-cell receptor (TCR)δ−1+, βF1− phenotype. They were CD5− (9 of 10) and CD4−/CD8− (9 of 10) or CD8+(1 of 10). A clonal γ-chain gene rearrangement was detected in all tested cases (9/9). All cases had an activated cytotoxic T-cell intracellular antigen-1 (TIA-1)+, Granzyme B+ phenotype. Epstein-Barr virus (EBV) sequences were detected in six cases by in situ hybridization (ISH). Despite an aggressive clinical course, complete remission was obtained in three patients, and one of the latter required a peripheral blood stem-cell transplantation. Nonhepatosplenic γδ peripheral T-cell lymphoma can be regarded as a model of activated cytotoxic lymphoma, occurring in mucosae or skin. These appear to be derived from the subpopulation of tissue-restricted γδ lymphocytes, which are involved in the host epithelial surface surveillance. The role of chronic antigen exposure in the pathogenesis of these rare lymphomas can be suggested, in view of the past history observed in at least some patients.