Risk factors for moderate-to-severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

AbstractAmong 810 consecutive hematopoietic stem cell transplantation (HSCT) patients, 679 survived more than 3 months and were evaluated for chronic GVHD. The aim of this study was to find predisposing factors increasing the risk of development of moderate-to-severe chronic GVHD. Many of the donors were HLA-identical siblings or related (n = 435), 185 were HLA-matched unrelated, and 59 were mismatched related or unrelated donors. Most of the patients had a hematological malignancy (n = 568), but 111 patients with a nonmalignant disease were included. Two hundred twenty-three patients (33%) developed mild, 41 (6%) moderate, and 15 (2.2%) severe chronic GVHD. The 5-year probability of development of moderate-to-severe chronic GVHD was 10%. We analyzed 30 potential risk factors for chronic GVHD. In the multivariate analysis, acute GVHD grades II to IV (relative hazard [RH], 2.30; 95% CI, 1.29- 4.10; P = .005), CML diagnosis (RH, 2.37; CI, 1.38-4.08; P = .002) and transplantation from an immunized female donor to a male recipient (RH, 2.16; CI, 1.14-4.11; P = .02) were independent risk factors for moderate-to-severe chronic GVHD. Recipient age also was significant (RH, 2.42; CI, 1.23-4.77; P = .01) if CML was not included in the analysis. In patients with no risk factors, the 5-year probability of development of moderate-to-severe chronic GVHD was 5%. In patients with 1 risk factor, the probability was 13%; 2 risk factors, 23%; and 3 risk factors, 45%. Among patients who developed chronic GVHD (n = 279), acute GVHD grades II to IV (RH, 2.18; CI, 1.23-3.86; P < .01) was the only predictive factor for moderate-to-severe chronic GVHD versus mild disease. Patients with previous acute GVHD grades II to IV may benefit from more aggressive initial treatment. This possibility would have to be examined in clinical trials.Biol Blood Marrow Transplant 2002;8(12):674-82

New apheresis techniques in transplantation

The shortage of organs for transplantation is a global problem and therefore it is of outmost importance to increase the number of donations and improve long term graft survival. As an effort to increase kidney donations, living kidney donors are being increasingly used and both patient and graft survival is superior after living donation compared with kidney transplantations using organs from deceased donors. If ABO incompatible kidney transplantations can be done, the pool of living kidney donors can theoretically be increased with 30-40%. Until recently ABO incompatible kidney transplantations could only be performed after a reinforced immunosuppressive protocol combined with splenectomy. These reinforced immunosuppressive protocols have had very limited use due to the significant side effects with increased morbidity as well as mortality. Therefore, in 2001 we introduced a new protocol that allows ABO incompatible kidney transplantation without splenectomy. The protocol includes rituximab to deplete B lymphocytes and to prevent rebound of antibodies post transplant, combined with a new antigen-specific apheresis technique for preoperative depletion of circulating anti-A/B antibodies. The new antigen-specific filter has been evaluated in 15 patients with the conclusion that this new technique is safe and that anti-A/B antibodies were efficiently depleted. The clinical outcome for the 15 patients was equal compared with ABO compatible kidney transplantation. The implementation of the protocol in other transplant centers revealed significant differences regarding preoperative anti-A/B titer levels using the semi-quantitative hemagglutination technique. Collaborative analysis showed that the differences were method-related due to the high variability of the tube hemagglutination technique. We showed that by standardization of the simple gel microcolumn hemagglutination technique, titer results can be reproducible enough to allow inter-center comparison of clinical results. Between September 2001 and September 2008, 45 patients have received ABO incompatible kidney transplantations at Karolinska University Hospital Huddinge with the new protocol. The first 20 kidney recipients were compared with a group of ABO compatible living donor kidney recipients. Mean follow-up was 3 years and the study showed that clinical outcome is similar after ABO incompatible kidney transplantation with this protocol compared with ABO compatible kidney transplantation, both short-term and long-term. The short term graft survival after kidney transplantation has improved much over the last decades but long term graft survival is still poor. In a pilot study, seven consecutive patients with biopsy-proven ongoing acute cellular rejections, which did not respond to conventional anti rejection treatment, were successfully treated with extracorporeal photopheresis (ECP), an immunomodulatory apheresis treatment. In a case control study with a 3-year follow up we aimed to investigate if prophylactic ECP can prevent rejection and improve clinical outcome after kidney transplantation. Because our patient groups are small, we regard the study mainly as a pilot study of safety. Event-free survival time was not different in the two groups and no ECP-related side effects were noted. An adaptive immune response with a tolerogenic shift was induced during ECP treatment with a significant increase of CD4+CD25hiFoxP3+ regulatory T cells. These two approaches to combat the organ shortage a) will increase the number of living kidney donations and b) shows promise as a tolerogenic immunomodulatory therapy

Older adult's experience of chronic low back pain and its implications on their daily life : Study protocol of a systematic review of qualitative research

Background: Of various chronic diseases, low back pain (LBP) is the most common and debilitating musculoskeletal condition among older adults aged 65 years or older. While more than 17 million older adults in the USA suffer from at least one episode of LBP annually, approximately six million of them experience chronic LBP that significantly affects their quality of life and physical function. Since many older adults with chronic LBP may also have comorbidities and are more sensitive to pain than younger counterparts, these older individuals may face unique age-related physical and psychosocial problems. While some qualitative research studies have investigated the life experiences of older adults with chronic LBP, no systematic review has integrated and synthesized the scientific knowledge regarding the influence of chronic LBP on the physical, psychological, and social aspects of lives in older adults. Without such information, it may result in unmet care needs and ineffective interventions for this vulnerable group. Therefore, the objective of this systematic review is to synthesize knowledge regarding older adults’ experiences of living with chronic LBP and the implications on their daily lives.Methods/design: Candidate publications will be sought from databases: PubMed, CINAHL, and PsycINFO. Qualitative research studies will be included if they are related to the experiences of older adults with chronic LBP. Two independent reviewers will screen the titles, abstracts, and full-text articles for eligibility. The reference lists of the included studies will be checked for additional relevant studies. Forward citation tracking will be conducted. Meta-ethnography will be chosen to synthesize the data from the included studies. Specifically, the second-order concepts that are deemed to be translatable by two independent reviewers will be included and synthesized to capture the core of the idiomatic translations (i.e., a translation focusing on salient categories of meaning rather than the literal translation of words or phrases).Discussion: This systematic review of qualitative evidence will enable researchers to identify potential unmet care needs, as well as to facilitate the development of effective, appropriate, person-centered health care interventions targeting this group of individuals.Systematic review registration: PROSPERO 2018: CRD4201809129

Additional file 3: of Older adult’s experience of chronic low back pain and its implications on their daily life: Study protocol of a systematic review of qualitative research

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Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P &lt; .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.De två första författarna delar förstaförfattarskapet.</p

Improved Survival after Allogeneic Hematopoietic Stem Cell Transplantation in Recent Years. A Single-Center Study

We analyzed the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) over the past 2 decades. Between 1992 and 2009, 953 patients were treated with HSCT, mainly for a hematologic malignancy. They were divided according to 4 different time periods of treatment: 1992 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009. Over the years, many factors have changed considerably regarding patient age, diagnosis, disease stage, type of donor, stem cell source, genomic HLA typing, cell dose, type of conditioning, treatment of infections, use of granulocyte-colony stimulating factor (G-CSF), use of mesenchymal stem cells, use of cytotoxic T cells, and home care. When we compared the last period (2006-2009) with earlier periods, we found slower neutrophil engraftment, a higher incidence of acute graft-versus-host disease (aGVHD) of grades II-IV, and less chronic GVHD (cGHVD). The incidence of relapse was unchanged over the 4 periods (22%-25%). Overall survival (OS) and transplant-related mortality (TRM) improved significantly in the more recent periods, with the best results during the last period (2006-2009) and a 100-day TRM of 5.5%. This improvement was also apparent in a multivariate analysis. When correcting for differences between the 4 groups, the hazard ratio for mortality in the last period was 0.59 (95% confidence interval [CI]: 0.44-0.79; P < .001) and for TRM it was 0.63 (CI: 0.43-0.92; P = .02). This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years