After myeloablative treatment and allogeneic stem cell transplantation (SCT), patients are kept in isolation rooms in the hospital to prevent neutropenic infections. During a 3-year period, patients were given the option of treatment at home after SCT. Daily visits by an experienced nurse and daily phone calls from a physician from the unit were included in the protocol. We compared 36 patients who wished to be treated at home with 18 patients who chose hospital care (control group 1). A matched control group of 36 patients treated in the hospital served as control group 2. All home care patients had hematologic malignancies and 19 were in first remission or first chronic phase. Of the donors, 25 were unrelated. The patients spent a median of 16 days at home (range, 0-26 days). Before discharge to the outpatient clinic after SCT, patients spent a median of 4 days (range, 0-39 days) in the hospital. In the multivariate analysis, the home care patients were discharged earlier (relative risk [RR] 0.33, P ؍ .03), had fewer days on total parenteral nutrition (RR 0.24, P < .01), less acute graft-versus-host disease (GVHD) grades II-IV (RR 0.25, P ؍ .01), lower transplantationrelated mortality rates (RR 0.22, P ؍ .04), and lower costs (RR 0.37, P < .05), compared with the controls treated in the hospital. The 2-year survival rates were 70% in the home care group versus 51% and 57% (not significant) in the 2 control groups, respectively (P < .03). To conclude, home care after SCT is a novel and safe approach. This study found it to be advantageous, compared with hospital care. (Blood. 2002;100: 4317-4324)
Summary:Three different types of anti-T cell antibody were used in patients undergoing haematopoietic stem cell transplantation (HSCT) with an HLA-A, -B and -DR compatible unrelated donor: ATG-Fresenius (ATG-F) (n = 26), Thymoglobuline (TMG) (n = 61) and OKT-3 (n = 45). The groups were comparable regarding diagnosis, stage, age, conditioning and GVHD prophylaxis, Adverse events were less frequent after ATG-F treatment. Levels of IL-2, IL-6, IFN-␥, TNF-␣ and GM-CSF were increased after OKT-3 infusion. In multivariate analysis OKT-3 treatment (P = 0.01), G-CSF treatment (P = 0.02) and a cell dose у2.7 ؋ 10 8 /kg (P = 0.03) gave a faster engraftment. Acute GVHD grades II-IV occurred in 25% of the ATG-F patients, 12% of the TMGpatients and 43% (P Ͻ 0.001 vs TMG) of the OKT-3 patients. OKT-3 was associated with acute GVHD in multivariate analysis. TRM was 26% using TMG as compared to 43% in the OKT-3 group (P = 0.03). Patient survival at 4 years was 63%, 50% and 45% in the ATG-F, TMG and OKT-3-treated patients, respectively (NS). Relapses were 8%, 49% and 34%, respectively (ATG-F vs TMG, P = 0.03). Relapse-free survivals were 61%, 40% and 37% (NS). Among CML patients the probability of relapse was 61% in TMG-treated patients, while no patients relapsed in the other two groups. To conclude, the type of anti-T cell antibody affects GVHD and relapse after HSCT using unrelated donors.
Summary:We have evaluated whether allogeneic hematopoietic stem cell transplantation (HSCT) could induce an antitumor effect in patients with metastatic solid tumors. A total of 12 HLA-identical siblings and 6 HLA-A-, -B-and -DRb1-compatible unrelated grafts were used. Diagnoses were adenocarcinoma of kidney (n ¼ 10), colon (n ¼ 6), breast (n ¼ 1) and cholangiocarcinoma (n ¼ 1). Conditioning was fludarabine 30 mg/m 2 /day for 3 days and 2 Gy of total body irradiation. Recipients of unrelated HSCT were also given thymoglobuline and two additional days of fludarabine. The median CD34+ cell dose was 7.5 Â 10 6 / kg. Immunosuppression was mycophenolate mofetil and cyclosporin. Among all, 12 patients became complete donor chimeras within a median of 28, 29 and 65 days for B, myeloid and T cells, respectively. Two patients rejected the grafts, one developed marrow aplasia and three were mixed chimeras. The probability of grades II-IV acute graft-versus-host-disease (GVHD) was 57%. Regression of all tumor metastases was seen in one patient with colon carcinoma. Another patient with colon and two with renal carcinoma had regression of lung metastases, but progression of metastases in the liver and/or bone. Necrosis of lung metastasis was found in one further patient with renal carcinoma who died of graft-versushost-disease (GVHD). In all, 10 patients died; four of transplant-related complications, one of trauma and five of progressive disease. Thus, progression was common after allogeneic HSCT in unselected patients with advanced solid tumors. However, the regression of some metastases associated with GVHD provides suggestive evidence that the GVHD effect may occur in renal and colon adenocarcinoma using reduced intensity conditioning. The immune system is known to induce tumor regression. 1 Following allogeneic hematopoietic stem cell transplantation (HSCT), graft-versus-host disease (GVHD) has been found to contribute to an antileukemic effect. 2,3 An alloresponse of donor T lymphocytes is most probably the cause of GVHD and the graft-versus-leukemia (GVL) effect. 4 An allogeneic graft-versus-tumor (GVT) effect has also been reported in breast and renal metastatic carcinoma. [5][6][7][8][9] When performing HSCT, lethal myeloablative conditioning to eradicate leukemia and induce marked immunosuppression to pave the way for the donor immunohematopoietic system has been the routine for several decades 10À13 . However, this approach has been challenged by using lower doses and less toxic conditioning to induce immunosuppression and take advantage of the GVT effect later rather than the antitumor effect of chemoradiotherapy. [14][15][16][17][18][19]
Among 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.
Summary:Three patients developed veno-occlusive disease of the liver (VOD) after allogeneic stem cell transplantation. On the day after diagnosis, N-acetylcysteine (NAC) was given, initially in loading doses and thereafter 50-150 mg/kg/day for 12 to 31 days. The maximum bilirubin levels were 137, 58 and 138 mmol/l in the three patients, respectively. After the introduction of NAC, bilirubin, aspertate aminotransferase, sIL-2 receptor and IL-8 decreased. All three patients achieved normal bilirubin levels and prothrombin times. To conclude, NAC may be useful for treatment of VOD. Bone Marrow Transplantation (2000) 25, 993-996.
We report the clinical outcome and results of chimaerism analysis in various cell lineages of 30 patients given non‐myeloablative conditioning, followed by allogeneic stem cell transplantation (SCT). The commonest diagnoses were chronic myelogenous leukaemia (n = 11) and solid tumours (n = 11). Twenty‐one patients received SCT from human leucocyte antigen (HLA)‐identical siblings and nine from matched unrelated donors. Median patient age was 53 (28–77) years. Four non‐myeloablative protocols were used, including fludarabine (30 mg/m2 × 3–6), busulphan (4 mg/kg × 2), cyclophosphamide (Cy) (30 mg/kg/day × 2) or total body irradiation (2 Gy), and anti‐thymocyte globulin. The patients were analysed by polymerase chain reaction (PCR) analysis of minisatellites on days 14, 21 and 28, then every other week up to 3 months and monthly thereafter. All samples were cell separated for T, B and myeloid cells using immunomagnetic beads. Eighteen patients were alive at a median follow‐up of 11 (6–20) months. Acute graft‐versus‐host disease (GVHD) occurred in 22 patients. Eighteen of the 22 patients with acute GVHD showed mixed chimaerism (MC) in the T‐cell fraction at the time of acute GVHD. However, all patients with acute GVHD showed donor chimaerism (DC) in the T‐cell fraction median 76 (7–414) days after onset versus three out of eight patients without acute GVHD, P < 0·001]. Disease response was diagnosed in 15 patients, median 100 (37–531) days after SCT. At the time of disease response, six out of15 patients showed MC in the T‐cell fraction. In conclusion, mixed chimaerism in the T‐cell fraction is common at the time of acute GVHD and disease response in patients conditioned with non‐myeloablative therapy.
Summary:Allogeneic stem cell transplantation (ASCT) has proved to have an important immune-mediated anti-tumour effect in patients with haematologic malignancies. There is also evidence of such an effect in patients with malignant tumours. We studied this effect of ASCT in a patient with colorectal cancer. A 77-year-old man having a primarily resected colonic cancer with disseminated lymph node involvement received ASCT from his HLA-identical sibling as the only treatment. Keywords: allogeneic stem cell transplantation; graftversus-host disease; colonic carcinoma; graft-versustumour; mixed chimerism Cancer may be controlled by the immune system as shown in experimental animal studies and in man. [1][2][3] Patients with leukaemia who develop acute graft-versus-host disease (GVHD) and, especially chronic GVHD, run a lower risk of relapse than those without GVHD. 4-6 Furthermore, T cell depletion of the graft, which effectively prevents GVHD, increases the risk of relapse. 7-9 A graft-versus-tumour (GVT) effect has been found in animal models, 10 Recently, more attention has been paid to the use of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell transplantation. Comparison of G-CSF-mobilized ASCT (containing at least a 10-fold increase in donor T cell numbers) and traditional bone marrow transplantation reveals a similar incidence of GVHD and graft-versus-leukaemia (GVL) effect. [16][17][18][19] Since donor T cells are the effectors of the GVL effect, it is important to study whether G-CSF-mobilized allogeneic stem cells maintain a reasonably high antitumour effect, as also in other malignancies, with a minimum of GVHD.We wished to study the clinical contributions of the GVT effect and GVHD in a patient with colonic cancer after nonmyeloablative ASCT. Materials and methods Patient and donorA 77-year-old man, who had undergone peripheral vascular surgery and coronary by-pass surgery, was diagnosed as having sigmoid cancer and underwent a left-sided hemicolectomy in April 1998. Histopathological examination revealed an adenocarcinoma Dukes C, with metastases in six of 12 local lymph nodes. With his history of severe vascular disease, he was not considered a candidate for adjuvant cytostatic therapy. At 1-year follow-up, he was found to have enlarged coeliac lymph nodes and a needle biopsy confirmed metastatic adenocarcinoma. As he had several healthy siblings, he was given the option of undergoing ASCT and was ultimately found to have a wellsuited donor in his healthy 66-year-old HLA-identical brother. ASCT for metastatic colonic carcinoma using nonmyeloablative conditioning was approved by the ethics committee at Huddinge University Hospital. Allogeneic stem cell transplantationThe patient received fludarabine (30 mg/m 2 ) i.v. on days −4, −3 and −2 before transplantation. On the day of trans-
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