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At least 343 records · Page 19Linked to original sources
PubMed1992

Transfer of specific immunity from donor to recipient of an allogeneic bone marrow graft: effect of conditioning on the specific immune response of the graft recipient.

Transfer of specific immunity was investigated in a group of 28 paediatric and adult leukaemia patients during the first 100 d after allogeneic bone marrow transplantation (BMT). These patients and/or their donors were immunized 7-13 d before transplantation with the recall antigen tetanus toxoid (TT) and the neo-antigen Helix pomatia haemocyanin (HPH). The recipients were booster immunized with both antigens at day 42 after transplantation. Transfer of a primary IgM and IgG response to HPH was successful in most paediatric and adult patients, but transfer of a secondary response to TT was established in only a few paediatric recipients. After booster immunization at day 42 most paediatric recipients responded with a rise in serum antibody titre to HPH as opposed to only two of 18 adult recipients. This incapability of the adult recipients to mount a secondary immune response may be related to their conditioning regimen which included Campath-IG in vivo. The results from this study indicate that transfer of immunity against recall- and neo-antigens is possible. However, the establishment of long-term memory may be affected by the regimen used to condition the graft recipient.

Adolescent↗
PubMed1993

The management of recurrent acute myelogenous leukaemia at a single centre over a fifteen-year period.

One hundred and sixty-two patients initially treated at St Bartholomew's Hospital between 1974 and 1988 developed recurrent acute myelogenous leukaemia (AML). In the majority, the intention was to administer intensive chemotherapy again; 22/162 were re-treated palliatively. A second complete remission (CR) was achieved in 50/126 (40%) evaluable patients. Several different regimens were employed over this time period; the treatment used was the only factor that correlated with achievement of second CR (P = 0.04). Ten of the 50 patients received myeloablative therapy with either allogeneic or autologous bone marrow transplantation in second CR. The median duration of second CR for those patients who did not proceed to intensive consolidation with bone marrow transplantation was 7 months. There was no correlation between second remission duration and age, or with the administration of either intensive or conventional consolidation therapy. The median survival from first recurrence for all patients was 4 months, increasing to only 5 1/2 months for those re-treated with chemotherapy and to 12 months for those patients in whom a second CR was achieved, confirming the very poor prognosis of these patients.

Adolescent↗
PubMed1993

Acute hepatitis C infection in patients undergoing therapy for haematological malignancies: a clinical and virological study.

Patients receiving multiple transfusions are at risk of acquiring hepatitis C (HCV) infection from a donor population which is unscreened for hepatitis C antibodies (anti-HCV). Prior to the introduction of blood donor screening for anti-HCV in the U.K., a group of patients undergoing therapy for haematological malignancies, with repeatedly abnormal liver function tests, were investigated for acute HCV infection. Thirty-two patients had repeatedly raised serum transaminases, and eight of these (25%) had evidence of an acute HCV infection. The diagnosis was made by the detection of HCV-RNA in the patients' serum using a complementary DNA/polymerase chain reaction (cDNA/PCR) procedure. All eight patients had received myeloablative chemotherapy and three had undergone bone marrow transplantation. HCV infection contributed significantly to the morbidity of this group of patients in the short term whilst they were undergoing treatment for their underlying haematological condition. The long-term effects have yet to be evaluated. In an attempt to decrease hepatic damage due to HCV, three patients were placed on interferon therapy. None showed a sustained reduction in serum transaminases or HCV viraemia. It is hoped that the introduction of anti-HCV screening of blood donors, will reduce the frequency of transfusion-acquired HCV infections. Early observations suggest that this is the case, as we have seen no new cases of HCV infection in our unit since the introduction of donor screening in September 1991.

Acute Disease↗
PubMed2005

Successful bone marrow transplantation in a patient with c-mpl-mutated congenital amegakaryocytic thrombocytopenia from a carrier donor.

Congenital amegakaryocytic thrombocytopenia (CAMT) is characterized by severe thrombocytopenia and the absence of megakaryocytes in bone marrow. Furthermore, mutation of the c-mpl gene has been identified as a cause of this disorder. The only curative treatment is allogeneic stem cell transplantation (SCT). The current report describes a patient exhibiting c-mpl mutation in both alleles who underwent transplantation of allogeneic bone marrow donated by her brother, a c-mpl mutated carrier, employing a fludarabine-based conditioning regimen. Engraftment and reconstitution of hematopoietic cells was rapid and without complications. These findings suggest that the carrier donor displaying the c-mpl mutation can serve as a donor source for SCT.

Bone Marrow Purging↗
PubMed1997

Hodgkin and non-Hodgkin lymphoma: local-regional radiation therapy after bone marrow transplantation.

PURPOSE: To assess the acute toxicity and therapeutic effect of local-regional radiation therapy after bone marrow transplantation performed for lymphoma in resistant relapse. MATERIALS AND METHODS: Twenty-one patients with Hodgkin (n = 12) or non-Hodgkin lymphoma (n = 9) underwent local-regional radiation therapy after bone marrow transplantation. Posttransplantation radiation was delivered to the dominant site of pretransplantation disease. Three patients with Hodgkin lymphoma and four with non-Hodgkin lymphoma underwent radiation therapy for posttransplantation recurrence. Total body irradiation was used in 10 patients. Mean radiation dose was lower in patients who underwent total body irradiation than in those who did not (P = .05). RESULTS: Nineteen of 21 patients completed local-regional therapy. Nonhematologic toxicity was mild in 20 patients. Hematologic toxicity was severe in five patients, four of whom began radiation therapy with low platelet counts. In-field disease progression occurred in six of 15 patients with relapse, including four with disease progression at the start of radiation therapy. Median progression-free survival was 12 months in patients with Hodgkin lymphoma and 1 month in patients with non-Hodgkin lymphoma. CONCLUSION: Posttransplantation local-regional radiation therapy can be safely administered in patients with lymphoma. Severe hematologic toxicity is a concern, however, in patients with low platelet counts.

Adolescent↗
PubMed1992

High-dose carmustine, etoposide, and cisplatin and autologous bone marrow transplantation for relapsed and refractory lymphoma.

PURPOSE: We determined the toxicity and efficacy of a new preparative autologous bone marrow transplantation (ABMT) regimen in patients with relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's disease. PATIENTS AND METHODS: Forty-four non-Hodgkin's lymphoma and 35 Hodgkin's disease patients 16 to 63 years of age were given intravenous carmustine (BCNU) 600 to 1,050 mg/m2, etoposide 2,400 to 3,000 mg/m2, and cisplatin 200 mg/m2 (BEP) and ABMT. Fifty-nine patients also received 15 to 20 Gy local radiation (involved-field radiotherapy [RI]) to active or previously bulky (> 5 cm) disease sites. RESULTS: Nonhematologic toxicities included nausea, vomiting, high-tone hearing loss, stomatitis, esophagitis, diarrhea, and hepatic and pulmonary toxicity. Two patients died within 40 days of marrow infusion as a result of sepsis and one patient died 7 months after transplant as a result of pulmonary fibrosis. Complete remissions (CRs) were noted in 72% (n = 57) of patients (n = 33 non-Hodgkin's lymphoma; n = 24 Hodgkin's disease). Forty patients (51%) remained alive and disease-free (n = 24 non-Hodgkin's lymphoma; n = 16 Hodgkin's disease) at a median of 17 (range, 8 to 57) months after marrow reinfusion. CONCLUSIONS: This regimen seems to be effective for relapsed lymphoma patients whose disease continues to exhibit chemotherapy sensitivity (16 of 24 [67%] disease-free). Furthermore, this regimen seems to be effective in patients who have never attained a CR (seven of 19 [37%] disease-free).

Adolescent↗
PubMed1992

Prevention of graft-versus-host disease by selective depletion of CD6-positive T lymphocytes from donor bone marrow.

PURPOSE: Acute and chronic graft-versus-host disease (GVHD) continues to be the major causes of morbidity and mortality after allogeneic bone marrow transplantation (BMT). In this study, we have evaluated the clinical effects of selective in vitro T-cell depletion of donor allogeneic bone marrow by using a single monoclonal antibody ([MoAb] anti-T12, CD6) and rabbit complement. This antibody recognizes mature T cells, but not other cellular elements such as natural-killer (NK) cells, B cells, and myeloid precursors. PATIENTS AND METHODS: From August 1983 to April 1991, 112 consecutive adult patients with hematologic malignancies underwent BMT with bone marrow from HLA-identical sibling donors. Marrow was harvested and depleted of mature T lymphocytes ex vivo by the use of three rounds of incubation with an anti-T12 antibody and rabbit complement. The preparative regimen consisted of cyclophosphamide and fractionated total body irradiation (TBI) in 108 patients. No patients received prophylactic immune suppression post-BMT. Purgation by anti-T12 was used as the only method for the prevention of GVHD. RESULTS: Twenty patients (18%) developed acute GVHD (grade 2 to 4); only eight patients developed chronic GVHD. The incidence of GVHD did not increase significantly with age. Only three of 112 patients (2.7%) exhibited acute graft failure. One patient developed late graft failure that was associated with cytomegalovirus (CMV) infection. Within the subset of 50 patients who had not previously undergone unsuccessful conventional therapy (acute leukemia in first remission or chronic myelogenous leukemia [CML] in stable phase), we estimated by the Kaplan-Meier method that the probability of disease-free survival was 50% at 3 years post-BMT, with a median follow-up of 44 months. The treatment-related mortality rate in this group was only 14% and was independent of patient age. CONCLUSIONS: We conclude that selective in vitro T-cell depletion with an anti-T12 monoclonal antibody effectively reduces the incidence of both acute and chronic GVHD after allogeneic BMT without compromising engraftment. Moreover, depletion of CD6-positive cells from donor marrow obviates the need to administer immune suppressive medications to the majority of patients. This approach reduces the morbidity and mortality of allogeneic BMT and permits the BMT of older patients.

Adult↗
PubMed1994

Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for recurrent follicular lymphoma.

PURPOSE: To assess myeloablative therapy with autologous bone marrow transplantation (ABMT) in younger patients with follicular lymphoma in the hope of prolonging remission duration and survival. PATIENTS AND METHODS: Since June 1985, 64 patients with follicular lymphoma have received cyclophosphamide (CY) 60 mg/kg x 2 and total-body irradiation (TBI) 2 Gy x 6 supported by ABMT as consolidation of second or subsequent remission. The marrow mononuclear cell (MNC) fraction was treated in vitro with three cycles of the monoclonal antibody (MAb) anti-CD20 and baby rabbit complement before cryopreservation. At the time of treatment, 34 patients were in complete remission (CR), and 30 had residual disease present. RESULTS: The median time to engraftment was 28 days (range, 15 to 46) for both a neutrophil count greater than 0.5 x 10(9)/L and a platelet count greater than 20 x 10(9)/L. Engraftment did not occur in one patient who died at 12 weeks, and three patients (excluded from the range) have had delayed recovery (> 6 months) of RBCs and platelets. Fifty two patients are alive; three died as a consequence of the transplant procedure, two died in remission from other causes, and seven died of recurrent lymphoma. There was a significant correlation between survival and the total number of episodes of treatment required during the course of the illness (< or = to three v > three, P = .01). With a median follow-up duration of 3 1/2 years, 35 patients continue in remission between 1 and 8 years, and 24 have developed recurrent lymphoma, five with evidence of transformation to high-grade histology. Freedom from recurrence did not correlate with the time from diagnosis, the number of previous treatments, the presence or absence of residual disease at the time of treatment, or during which specific remission the treatment was given (second v > second). However, comparison with an age-matched, remission-matched, historical control group shows a significant advantage in favor of treatment with CY plus TBI plus ABMT (P = .001); currently, there is no difference in survival. CONCLUSION: These results are encouraging, although preliminary; it remains to be established whether this treatment prolongs survival.

Adult↗
PubMed1995

Busulfan/cyclophosphamide as conditioning regimen for allogeneic bone marrow transplantation for myelodysplasia.

PURPOSE: A non-radiation-containing regimen of busulfan and cyclophosphamide (BU/CY) was evaluated for toxicity, relapse, and long-term survival in patients who received allogeneic bone marrow transplantation (BMT) for myelodysplasia (MDS). PATIENTS AND METHODS: Thirty-eight patients with MDS, including eight with therapy-related MDS, were prepared for BMT using BU/CY. RESULTS: Fourteen patients remain in first remission 18 to 60 months posttransplant. Five patients relapsed after BMT, and four of these patients died. Eight additional patients died of acute or chronic graft-versus-host disease (GVHD), and 11 died of regimen-related toxicity, primarily systemic mycoses. Overall survival rate at 2 years was 45% (95% confidence interval [CI], 0.30 to 0.61), with a 24% probability of relapse (95% CI, 0.10 to 0.49). Regimen-related toxicity was manifested primarily as hepatic dysfunction in 72% of patients, with 16% developing overt venoocclusive disease (VOD). CONCLUSION: Non-radiation-containing preparative regimens offer long-term survival in allogeneic BMT for MDS that is comparable to that of radiation-containing regimens, and are useful in patients with therapy-related MDS. Monitoring BU levels may reduce regimen-related mortality and improve survival.

Adolescent↗
PubMed1995

Predictive factors for peripheral-blood progenitor-cell collections using a single large-volume leukapheresis after cyclophosphamide and granulocyte-macrophage colony-stimulating factor mobilization.

PURPOSE: (1) To study the ability of mobilized peripheral-blood progenitor cells (PBPC) collected in a single large-volume leukapheresis performed on a predetermined date to accelerate engraftment after high-dose cyclophosphamide and thiotepa; (2) to establish the minimum dose of PBPC associated with early engraftment; and (3) to identify parameters predictive of collection of large numbers of PBPC. PATIENTS AND METHODS: Twenty-three patients with breast cancer received cyclophosphamide (4 g/m2) and granulocyte-macrophage colony-stimulating factor ([GM-CSF] 5 micrograms/kg/d x 15 days) for PBPC mobilization. A single leukapheresis was performed 15 days after cyclophosphamide administration. Then, patients received high-dose cyclophosphamide and thiotepa followed by reinfusion of PBPC and 4-hydroperoxycyclophosphamide (4HC)-purged bone marrow. PBPC concentration was measured in serial peripheral-blood samples and in the leukapheresis product. Correlation analysis between PBPC dose and engraftment and between leukapheresis yield and patient characteristics was attempted. RESULTS: A single leukapheresis processed a median 36 L (range, 24 to 46) blood and collected 5 x 10(6) CD34+ cells/kg (< 0.3 to 24) and 6.2 x 10(5) colony-forming units granulocyte-macrophage (CFU-GM)/kg (< 0.001 to 29). All sixteen patients (70%) reinfused with > or = 2.9 x 10(6) CD34+ cells/kg reached a level of greater than 1,000 leukocytes/microL by day 13 and greater than 50,000 platelets/microL by day 15. All of these patients had a percentage of peripheral-blood CD34+ cells > or = 0.5%, and all but one, a level of greater than 100,000 platelets/microL, on the day of leukapheresis. The bone marrow CD34+ cell percentage at study entry predicted the number of CD34+ cells collected after PBPC mobilization (R2 = .42, P = .002). All patients with > or = 2.5% bone marrow CD34+ cells experienced early engraftment. CONCLUSION: Reinfusion of PBPC collected in a single leukapheresis accelerates engraftment in the majority of patients. Pretreatment bone marrow CD34+ cell content determines PBPC mobilization capacity and may help select hematopoietic rescue strategies.

Adult↗