Britt-Marie Svahn

Low incidence of acute graft-versus-host disease, using unrelated HLA-A-, HLA-B-, and HLA-DR-compatible donors and conditioning, including anti-T-cell antibodies.

BACKGROUND Using unrelated bone marrow, there is an increased risk of graft-versus-host disease (GVHD). METHODS HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow was given to 132 patients. The diagnoses included chronic myeloid leukemia (n=43), acute lymphoblastic leukemia (n=29), acute myeloid leukemia (n=27), myelodysplastic syndrome (n=4), lymphoma (n=3), myeloma (n=1), myelofibrosis (n=1), severe aplastic anemia (n=12), and metabolic disorders (n=12). The median age was 25 years (range 1-55 years). HLA class I was typed serologically, and class II was typed by polymerase chain reaction using sequence-specific primer pairs. Immunosuppression consisted of antithymocyte globulin or OKT3 for 5 days before transplantation and methotrexate combined with cyclosporine. RESULTS Engraftment was seen in 127 of 132 patients (96%). Bacteremia occurred in 47%, cytomegalovirus (CMV) infection in 49%, and CMV disease in 8%. The cumulative incidences of acute GVHD > or = grade II and of chronic GVHD were 23% and 50%, respectively. The 5-year transplant-related mortality rate was 39%. The overall 5-year patient survival rate was 49%; in patients with metabolic disorders and severe aplastic anemia, it was 61% and 48%, respectively. The disease-free survival rate was 47% in patients with hematological malignancies in first remission or first chronic phase and 38% in patients with more advanced disease (P=0.04). Acute GVHD was associated with early engraftment of white blood count (P=0.02). Poor outcome in multivariate analysis was associated with acute myeloid leukemia (P=0.01) and CMV disease (P=0.04). CONCLUSION Using HLA-A-, HLA-B-, and HLA-DR-compatible unrelated bone marrow and immunosuppression with antithymocyte globulin, methotrexate, and cyclosporine, the probability of GVHD was low and survival was favorable.

BK-viruria and haemorrhagic cystitis are more frequent in allogeneic haematopoietic stem cell transplant patients receiving full conditioning and unrelated-HLA-mismatched grafts

The influence of conditioning regimen, donor background and HLA matching on development of BK virus (BKV)-associated haemorrhagic cystitis (HC) was examined in 175 allogeneic haematopoietic stem cell transplant (HSCT) patients, undergoing 179 HSCT events. Twenty-seven patients presented late-onset HC, and BK viruria was verified in 23/27 HC events. Seventy-one (40%) HSCTs were performed with myeloablative conditioning (MC), 108 (60%) were performed with reduced intensity conditioning (RIC), 66 (37%) were performed with a related donor (RD) grafts and 113 (63%) with an unrelated donor (URD) graft. BK viruria was more common during HC, than non-HC events, after MC as compared to RIC (both P<0.001), and with an HLA-mismatched donor (P<0.01). By multivariate logistical regression analysis, independent risk factors for HC were BKV (OR 6.7; 95% CI 2.0–21.7; P=0.001), MC (OR 6.0; 95% CI 2.1–17.3; P<0.001) and URD (OR 3.4; 95% CI 1.1–10.6; P=0.03). However, when analysing HSCT performed with URD or RD grafts separately, BKV (OR 8.5; 95% CI 1.8–19.3; P=0.004) and MC (OR 5.9; 95% CI 1.3–11.3; P=0.009) increased the risk for HC only with a URD, but not with an RD graft.

Allogeneic hematopoietic stem cell transplantation for inherited disorders : Experience in a single center

Background. Allogeneic hematopoietic stem cell transplantation (ASCT) is a possible cure for many inherited disorders. Methods. We report 20 years of experience in 71 patients. The disorders include 7 immunodeficiencies, 21 hematological disorders, 13 histiocytic disorders, 9 mucopolysaccharoidoses, 7 metachromatic leukodystrophies (MLD), 3 adrenoleukodystrophies (ALD), 2 adrenomyeloneuropathy (AMN), 6 patients with Gaucher’s disease, 1 Sandhoff’s disease, and 2 patients with aspartylglucosaminuria. Their median age was 4 (0-39) years. The donors were 29 HLA-identical related, 27 matched unrelated (MUD) and 15 HLA mismatches. Results. In recipients of HLA-identical sibling grafts, none developed acute GVHD grades II-IV as against 22% in all others. The overall cumulative incidence of chronic GVHD was 17%. The 5-year survival rates were 93%, 84%, and 46% in recipients of grafts from HLA-identical siblings, MUD and HLA-mismatches, respectively. The overall 10-year survival rate was 69%. All of the surviving patients with immunodeficiencies and hemoglobinopathies are well. Four patients with Hurler’s disease are also well, apart from skeletal problems. Five patients with Gaucher’s disease are between 14 and 22 years after the transplant. Two infants with MLD deteriorated, a girl with the juvenile form has stable disease and one woman with the adult form has improved. Among four survivors with ALD/AMN, three are well and one has dementia. Two patients with aspartylglucosaminuria have stable disease. Conclusion. In patients with inborn errors of metabolism, ASCT gives a high survival rate using HLA-matched donors. Beneficial effects are seen in those who are transplanted early.

Intraosseous compared to intravenous infusion of allogeneic bone marrow

Thirty-eight patients (⩾18 years) receiving marrow transplants from HLA-identical or one antigen- mismatched related donors were randomized to intraosseous (i.o.) + intravenous (i.v.) (n = 10), i.o. (n = 8) or i.v. (n = 20) infusions of bone marrow. There were no significant differences in patient characteristics. PMN/l more than 0.5 × 109 occurred on days 19 (median), 20 and 18.5 in the i.o. + i.v., i.o. and i.v. groups, respectively. We found a significant reduction in the number of days on total parenteral nutrition (P = 0.03) and a tendency to a reduction in the number of days on antibiotics (P = 0.06) in the i.o. compared to the i.v. group. Bacteraemia did not occur in the i.o. group, but was seen in 30% of the i.v. group (NS). The incidences of acute and chronic graft-versus-host disease, transplantation-related mortality, relapse and patient survival rates were similar in the three groups. Five patients examined with bone marrow scintigraphy showed the same distribution of granulocytes in the bone marrow directly after transplantation and 3 weeks after transplantation, whether the bone marrow was given by the i.o. or by the i.v. route. We conclude that allogeneic bone marrow transplantation can safely be performed by i.o. infusion, but haematopoietic recovery is not improved.

Hemorrhagic cystitis: a retrospective single-center survey.

Abstract:  Severe hemorrhagic cystitis (HC) may be a life‐threatening complication in allogeneic stem cell transplantation (SCT). In order to improve the strategies for prophylaxis and treatment, we retrospectively analyzed data on patients who underwent SCT at our center from 1990 through 2005. Patients with HC were identified through our database and their medical charts were reviewed. Grades 2–5 and 3–5 HC developed in 109/834 patients (13.1%) and 27/834 patients (3.2%), respectively. The frequency of HC decreased over the time from 18.0% in 1990–1992 to 9.5% in 2002–2005 (p = 0.005). HC started on a median of 35 (0–166) days post‐transplant and persisted for a median of 23 (2–270) days. Transplant‐related mortality was 21% in patients without HC, 15% in those with HC of grade 2, 55% in those with grade 3, and 71% in patients with HC of grades 4–5 (p < 0.001). In multivariate analysis, the risk factors for HC were myeloablative conditioning, busulphan, cytomegalovirus infection, hematological malignancy, and acute graft‐versus‐host disease (aGVHD). With four risk factors, the risk of HC development was 31%. Risk factors for severe HC of grades 3–5 were aGVHD and bacteremia.

Costs of allogeneic hematopoietic stem cell transplantation.

Background. This study aims to determine the total costs after allogeneic hematopoietic stem cell transplantation (ASCT) and factors associated with increases or decreases in costs. Methods. We collected all in- and outpatient costs during 5 years in 93 patients who had undergone ASCT in 1998 and 1999 at our unit. The inpatient costs included all those related to a patient from the first day of admission until discharge and then all costs of readmission in the Stockholm area. Results. The total median cost of five posttransplant years was 139,414 (52,095–345,640) euro (&U20AC;) or 167,296 US

Case-control comparison of at-home and hospital care for allogeneic hematopoietic stem-cell transplantation: the role of oral nutrition.

(the rate of 1&U20AC; is approximately

Is it safe to treat allogeneic stem cell transplant recipients at home during the pancytopenic phase? A pilot trial.

1.2). The costs were highest during the first year—median inpatient and outpatient costs 100,650&U20AC; and 13,066 &U20AC;, respectively. The total costs during the first year were higher in patients with acute graft-versus-host disease grades III-IV (relative hazards [RH] 1.35, P=0.003), bacteremia (RH 1.33, P=0.005), veno-occlusive disease of the liver (RH 1.32, P=0.005), prophylaxis with granulocyte colony-stimulating factor (G-CSF; RH 1.31, P=0.01), acute leukemia (RH 1.32, P=0.008), and treatment in hospital instead of at home (RH 1.20, P<0.07). During the early transplant period, a second transplantation (RH 1.28, P=0.014) and hemorrhagic cystitis (HC; RH 1.24, P=0.03) were also associated with higher costs. The total 5-year cost declined with longer survival rates (r=0.4028, P<0.001) and reduced intensity conditioning (RH 0.79, P=0.024). Conclusion. Higher costs of ASCT were associated with retransplantation, acute leukemia, G-CSF prophylaxis, hospital care, myeloablative conditioning, and major transplant-related complications.

Treatment costs and survival in patients with grades III-IV acute graft-versus-host disease after allogenic hematopoietic stem cell transplantation during three decades.

Background. Acute graft-versus-host disease (GVHD) was reduced using home care compared with hospital care after allogeneic hematopoietic stem-cell transplantation (ASCT). Methods. Between March 1998 and December 2006, 601 patients underwent ASCT at our unit. Requirements for at-home ASCT were fulfilled by 76 patients. A control group of 76 patients treated in the hospital were matched for age, sex, diagnosis, stage of disease, conditioning, stem-cell source, type of donor, and immunosuppression. Oral nutrition was determined as median kcal/kg/day for the first 21 days after ASCT. Results. The home-care patients received more oral nutrition per day than hospital controls (P<0.05). Number of days at home correlated with oral nutrition (P=0.004). In multivariate analysis, acute GVHD of grades II to IV was associated with poor oral nutrition (P=0.003) and hospital care (P=0.06). Transplant-related mortality was associated with acute GVHD grades II to IV (P<0.0001) and bacteremia (P=0.004). In addition to acute GVHD and bacteremia, death was associated with absence of chronic GVHD (P=0.012). Five-year survival was 65% in patients treated at home, when compared with 47% in the controls (P=0.04). Conclusion. Better oral nutrition may be one reason for the reduced probability of acute GVHD and better survival with at-home care than with hospital care.

Safety and Side Effects of Using Placenta-Derived Decidual Stromal Cells for Graft-versus-Host Disease and Hemorrhagic Cystitis

After myeloablative treatment and allogeneic stem cell transplantation (ASCT), patients are kept isolated in the hospital to prevent infections during neutropenia. To date, 22 patients have been given the choice of being treated at home. Eleven could not be treated at home, and they served as controls. Most had haematological malignancies. The donors were 12 HLA-compatible unrelated, nine HLA-identical siblings and one twin. In the home care group, three developed bacteraemia, compared to nine in the controls (P < 0.01). Patients in the home care group had fewer days of total parenteral nutrition (median 3 vs 24, P < 0.001), required fewer erythrocyte transfusions (median 4 vs 8, P = 0.01), fewer days on i.v. antibiotics (median 6 vs 13 days), and on analgesics (median 0 vs 15) than the controls (P < 0.05). Days with fever, time to engraftment, days with G-CSF and acute GVHD were the same in the two groups. Seven of 11 patients treated at home were readmitted to the ward for a median of 3 (0–7) days, due to fever or lack of a caregiver at home. Days to discharge to the out-patient clinic were faster in the group treated at home (median 20 vs 35 days, P < 0.01). Patients who were treated at home enjoyed being active and taking a walk when they felt like it. This preliminary report suggests that home care after ASCT is not only safe, but superior to isolation in the hospital. Bone Marrow Transplantation (2000) 26, 1057–1060.