Lewis rats that were given injections of 10(6) to 10(8) (Lewis X Brown Norway) F1 hybrid bone marrow cells produce predominantly, if not exclusively, 19S lymphocytotoxic antibodies. A number of Lewis rats that received transplants of perfused renal allografts from bone marrow donors at, or near, the peak of IgM response survival for well over 200 days with good renal function and no histological evidence of chronic rejection. All long-surviving rats had detectable lymphocytotoxic antibodies up to 120 days after allografting; late enhancing antibodies had the restricted specificity possibly identical or similar to anti-I region antisera. All rats bearing prolonged renal allografts were unable to accept donor-specific skin grafts or to respond with specific lymphocytotoxic antibodies following skin grafting. The possible involvement of non-complement-fixing 19S alloantibodies in active enhancement of rat renal allografts is discussed.
BACKGROUND: Allogeneic red blood cell transfusion is frequently used in total hip replacement surgery (THR). However, data on the prognosis of transfused patients are sparse. In this study we compared the risk of complications following THR in transfused and non-transfused patients. METHODS: A population-based follow-up study was performed using data from medical databases in Denmark. We identified 28,087 primary THR procedures performed from 1999 to 2007, from which we computed a propensity score for red blood cell transfusion based on detailed data on patient-, procedure-, and hospital-related characteristics. We were able to match 2,254 transfused with 2,254 non-transfused THR patients using the propensity score. RESULTS: Of the 28,087 THR patients, 9,063 (32.3%) received at least one red blood cell transfusion within 8 days of surgery. Transfused patients had higher 90-day mortality compared with matched non-transfused patients: the adjusted OR was 2.2 (95% confidence interval (CI): 1.2-3.8). Blood transfusion was also associated with increased odds of pneumonia (OR 2.1; CI: 1.2-3.8), whereas the associations with cardiovascular or cerebrovascular events (OR 1.4; CI: 0.9-2.2) and venous thromboembolism (OR 1.2; CI: 0.7-2.1) did not reach statistical significance. The adjusted OR of reoperation due to infection was 0.6 (CI: 0.1-2.9). CONCLUSIONS: Red blood cell transfusion was associated with an adverse prognosis following primary THR, in particular with increased odds of death and pneumonia. Although the odds estimates may partly reflect unmeasured bias due to blood loss, they indicate the need for careful assessment of the risk versus benefit of transfusion even in relation to routine THR procedures.
Six children (aged 9 months to 10 and 5/12 years) with hemophagocytic lymphohistiocytosis (HLH) have undergone allogeneic BMT in Sweden. In two of the children unrelated donors were used. Parents were available as donors in two of the cases and siblings in the other two. Conditioning before BMT consisted of etoposide, busulfan and cyclophosphamide with the addition of ATG in two cases and OKT 3 in one case. For post-transplant immunosuppression, i.v. methotrexate and cyclosporin A (CsA) were used in five cases, and in one child CsA was combined with methylprednisolone. Of the six children, four are alive and well 2 and 3/12 to 3 and 1/12 years after BMT. One child, who had an unrelated donor with one DR-antigen mismatch, died 30 days after BMT of fulminant grade IV GVHD. Another patients, seropositive for CMV, received marrow from an unrelated HLA-A, -B, -DR and -DP identical donor. After an initially uneventful course, CMV was isolated from her leukocytes. Seven months after BMT she developed a progressive obstructive chronic bronchiolitis and succumbed to respiratory insufficiency 14 months after the transplant. This study supports the view that BMT is the treatment of choice in HLH, particularly if an HLA-identical related donor is available.
We report a retrospective analysis of the experience of a single centre in treating severe aplastic anemia (SAA) with allogeneic bone marrow transplant (BMT). Between 1982 and 1992, we transplanted 21 patients with SAA (14 males, 7 females); median age at BMT was 15 y (range 2-40 y); median time from diagnosis of SAA to BMT was 29 d (range 6 d-5.5 y). Thirteen patients had received multiple transfusions before BMT. Patients were conditioned with cyclophosphamide 50 mg/kg for 4 d, +/- total body irradiation 300-500 cGy as a single fraction; 1 patient received total nodal irradiation (750 cGy) plus antithymocyte globulin. Sixteen patients received bone marrow from human leucocyte antigen (HLA)-identical siblings, 3 from haplo-identical parents, and 2 from unrelated volunteer donors; graft-versus-host disease (GVHD) prophylaxis was variable. Three patients failed to fully engraft following BMT; 2 achieved successful engraftment following a second BMT. Six of 20 evaluable patients (30%) developed grade II-IV acute GVHD, of whom 3 died; 3 patients developed limited and 5 patients (31%) developed extensive chronic GVHD, of whom 1 died. Fourteen patients (67%) are alive and well following BMT with a median follow-up of 6 y (range 2.1-11 y). Survival was superior in patients receiving sibling-donor BMT (75%) compared with those receiving parent- or unrelated-donor BMT (40%). We conclude that allogeneic BMT remains an important mode of treatment for SAA, but long-term survival remains limited by graft failure and GVHD.
Twenty-four patients with multiple myeloma received an allogeneic bone-marrow graft from HLA-compatible sibling donors (n = 23), or a twin donor (n = 1). Eighteen patients are alive, 1-36 months post bone-marrow transplantation (median 14 months). Ten of these patients had no signs of multiple myeloma as judged by immunoglobulins in serum, light chains in urine, or the percentage of plasma-cells in bone-marrow aspirate. Bone lesions on X-ray were mainly unchanged. Six patients died from transplant-related complications 3 weeks to 5 months post transplantation. One of these patients had severe acute graft-versus-host disease (aGVHD). In other patients aGVHD was a minor problem. Allogeneic bone-marrow transplantation appears to be a promising method for treatment of a selected group of patients with multiple myeloma.
A boy with Chédiak-Higashi syndrome (CHS) treated by allogeneic bone marrow transplantation (BMT) is described. He had had several respiratory infections during his first 2 years of life, and at the age of 2.5 years he presented with an accelerated phase of CHS. Despite treatment with ascorbic acid and trimethoprim/sulfamethoxazole, he continued to experience recurrent bacterial infections. Allogeneic BMT was performed with his HLA- and mixed leukocyte culture-identical healthy brother as the donor. The preparative regimen consisted of busulfan and cyclophosphamide, and methotrexate and cyclosporine A were given as prophylaxis for graft-versus-host disease (GVHD). The patient engrafted well, and no symptoms or signs of acute GVHD developed. He then achieved chimerism status, in which half the peripheral blood neutrophils and some of the bone marrow myelopoietic cells displayed Chédiak-Higashi granules, and DNA analysis showed half the peripheral blood cells to be of donor origin and the other half to be of host origin. The boy is currently alive and well 24 months after transplant. Allogeneic BMT, even with mixed chimerism as a result, is a potentially curative therapy for CHS.
Allogeneic bone marrow transplantation in first remission for children with very high-risk acute lymphoblastic leukemia: a retrospective case-control study in the Nordic countries. Nordic Society for Pediatric Hematology and Oncology (NOPHO).
Among children with high-risk (HR) ALL there are subgroups with very-high-risk (VHR) features and poor prognosis despite developments in conventional chemotherapy for childhood ALL. We evaluated the outcome of VHR-ALL in children receiving allogeneic BMT (allo-BMT) in first remission (1CR) in a retrospective case-control study. In the population-based ALL material of the five Nordic countries, 22 children with VHR-ALL have undergone allo-BMT in 1CR between 1981-1991. We compared the outcome in these 22 children with 44 closely matched control patients who received conventional chemotherapy on HR-ALL protocols, as well as with a group of 405 children representing the remaining HR-ALL patients in the Nordic ALL database. The disease-free survival at 10 years was 73% in children receiving allo-BMT in 1CR, 50% in the matched controls (P = 0.02), and 59% in the remaining HR-ALL patients. The good prognosis of the allo-BMT group was due to a low relapse rate of 9%, as opposed to 41% in the group of matched controls. The superiority of allo-BMT as therapy in 1CR was mainly apparent in those with a very high WBC of > or = 100 x 10(9)/I at diagnosis; in the allo-BMT group 9/10 survived, as opposed to 8/20 of the matched controls (P = 0.03). We conclude that allo-BMT in 1CR should be seriously considered for children with a matched sibling donor and a VHR-ALL with WBC of > or = 100 and other established VHR criteria.