A multi-centre retrospective analysis on 117 patients relapsing after bone marrow transplantation (BMT) for acute leukaemia was carried out by the Leukaemia Working Party of the European Group for Bone Marrow Transplantation (E.B.M.T.). Forty-one patients had acute myeloid leukaemia (AML) and 76 had acute lymphoblastic leukaemia (ALL). Relapse occurred between 3 and 30 months after BMT and where investigated the leukaemia was found to have relapsed in recipient cells. In 10 cases the relapse was associated with new cytogenetic abnormalities. 74 patients received further treatment for leukaemia. Of these 21 out of 50 with ALL and 11 out of 24 with AML achieved a complete remission and had a median survival of 12 months compared with a median survival of 4 months for untreated patients or patients not achieving complete remission (P less than 0.001). Factors predictive for successful remission induction were a long interval between bone marrow transplant and relapse in ALL patients; and isolated extramedullary relapse. Presenting blast count, karyotype and remission status and number at the time of BMT were not predictive. Donor bone marrow was shown to be responsible for haemopoietic recovery occurring in the 21 out of 31 patients tested who achieved remission using donor karyotype or red blood cell antigens as markers. Nine patients received a second bone marrow transplant but only one became a long-term survivor. The results show that chemotherapy can usually prolong survival in selected patients with acute leukaemia relapsing after BMT but further BMT has a poor outlook.
Summary:We investigated the impact of the most commonly used preparative regimens on the outcome of 395 patients with diffuse large cell lymphoma (DLCL), consecutively reported to the registry of the Spanish GEL/TAMO. Among them, 139 (35%) were autografted in 1st CR, 86 (22%) in 2nd/3rd CR, 124 (31%) had chemosensitive disease and 46 (12%) had chemoresistant disease. Conditioning consisted of chemotherapy-only in 348 patients (BEAM, 164; BEAC, 145; and CBV, 39) and radiochemotherapy with CY and TBI in 47. Median times to granulocyte, platelet recovery and to discharge were significantly shorter in the chemotherapy-only group. Early transplant-related mortality was significantly higher when using CY-TBI. After a median follow-up of 28 months, overall survival (OS) at 8 years of patients conditioned with BEAM or BEAC (58% (95% CI 50-66%)) was more favorable than with CBV (40% (95% CI 24-56%)), and significantly better than with CY-TBI (31% (95% CI 18-44%)). Multivariate analysis revealed that patients conditioned with chemotherapyonly regimens had improved OS, disease-free (DFS) and relapse-free survival (RFS) when compared to those conditioned with CY-TBI. Status at transplant was also a powerful prognostic indicator. We conclude that preparative regimens consisting of chemotherapy-only seem more efficacious than CY-TBI as conditioning for DLCL, because of faster engraftment and greater antilymphoma effect, as indicated by improved OS, DFS and RFS. Bone Marrow Transplantation (2001) 27, 405-412. Keywords: high-dose therapy; preparative regimens; non-Hodgkin's lymphoma; prognostic factors; diffuse large cell lymphoma Over the past two decades, high-dose therapy (HDT) followed by autologous stem-cell transplantation (ASCT) has been explored to improve the long-term outcome of patients with non-Hodgkin's lymphoma (NHL). Despite the many reports, a number of questions remain unanswered regarding the best transplantation technique in this spectrum of disorders.
The chemokine receptor CXCR4 has been implicated in the migration and trafficking of malignant B cells in several haematological malignancies. Over‐expression of CXCR4 has been identified in haematological tumours, but data concerning the role of this receptor in diffuse large B cell lymphoma (DLBCL) are lacking. CXCR4 is a marker of poor prognosis in various neoplasms, correlating with metastatic disease and decreased survival of patients. We studied CXCR4 involvement in cell migration in vitro and dissemination in vivo. We also evaluated the prognostic significance of CXCR4 in 94 biopsies of DLBCL patients. We observed that the level of expression of CXCR4 in DLBCL cell lines correlated positively with in vitro migration. Expression of the receptor was also associated with increased engraftment and dissemination, and decreased survival time in NOD/SCID mice. Furthermore, administration of a specific CXCR4 antagonist, AMD3100, decreased dissemination of DLBCL cells in a xenograft mouse model. In addition, we found that CXCR4 expression is an independent prognostic factor for shorter overall survival and progression‐free survival in DLBCL patients. These results show that CXCR4 mediates dissemination of DLBCL cells and define for the first time its value as an independent prognostic marker in DLBCL patients. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
Chronic graft-versus-host disease (GVHD)
Summary. Disparity for the minor histocompatibility antigen HA-1 between patient and donor has been associated with an increased risk of acute graft-versus-host disease (GvHD) after allogeneic human leucocyte antigen (HLA)-identical sibling donor stem cell transplantation (SCT). However, no data concerning the impact of such disparity on chronic GvHD, relapse or overall survival are available. A retrospective multicentre study was performed on 215 HLA-A2-positive patients who received an HLA-identical sibling SCT, in order to determine the differences in acute and chronic GvHD incidence on the basis of the presence or absence of the HA-1 antigen mismatch. Disease-free survival and overall survival were also analysed. We detected 34 patient±donor pairs mismatched for HA-1 antigen (15´8%). Grades II±IV acute GvHD occurred in 51´6% of the HA-1-mismatched pairs compared with 37´1% of the non-mismatched. The multivariate logistic regression model showed statistical significance (P: 0´035, OR: 2´96, 95% CI: 1´07±8´14). No differences were observed between the two groups for grades III±IV acute GvHD, chronic GvHD, disease-free survival or overall survival. These results confirmed the association between HA-1 mismatch and risk of mild acute GvHD, but HA-1 mismatch was not associated with an increased incidence of chronic GvHD and did not affect relapse or overall survival.
Our data indicate that the silencing of CDH13 expression by aberrant promoter methylation occurs at an early stage in CML pathogenesis and probably influences the clinical behavior of the disease.
Among 217 patients who received an allogeneic (136 cases) or autologous (81 cases) bone marrow transplant, the diagnosis of hepatic veno-occlusive disease (VOD) was established in 38 according to Seattle clinical criteria. Thirty-two underwent a transjugular liver biopsy and measurement of the hepatic venous pressure gradient (HVPG). The study was completed in 30 patients with no serious complications. Hepatic VOD was histologically confirmed in 18 patients (60%); the remaining 12 were classified as non-VOD. An increased HVPG discriminated well between VOD and non-VOD cases. Thus, hemodynamic data can considerably reinforce the accuracy of histological diagnosis. The predictive value of two vs. three clinical data of the Seattle criteria was analyzed. Among the 19 cases fulfilling two clinical data VOD was confirmed in only eight (42%), whereas VOD was proved in ten of 11 cases (91%) (p = 0.02) suspected on the basis of three clinical data. When reliability of the Baltimore clinical criteria was analyzed, the result was identical to that observed when three Seattle clinical data were present. The specificity of the latter classification was high (92%) while its sensitivity was relatively low (56%). In conclusion, clinical criteria are not reliable for either recognizing or excluding the diagnosis of VOD. Thus, a transjugular liver biopsy, associated with hemodynamic evaluation, is strongly recommended when VOD is clinically suspected.
Summary:mixed chimerism 5,6 and leukemic relapse, 7-10 especially in patients with chronic myelogenous leukemia (CML). Based on previous experiences in animals and humans,The role of the T cell subpopulations in aGVHD, graftlow doses of CD8 + lymphocytes infused together with versus-leukemia (GVL) effect and graft failure has been the marrow graft seem to enhance engraftment after studied in experimental animal models and in clinical proallogeneic T cell-depleted marrow transplantation.tocols of selective T cell depletion. [11][12][13][14] It is accepted that From April 1994 to February 1997, 12 patients with both CD4 + and CD8 + lymphocytes are involved in the allochronic myelogenous leukemia in first chronic phase reactive response after BMT, causing aGVHD. 15 Selective receiving a bone marrow transplant (BMT) from an depletion of CD8 + cells from the marrow graft in combi-HLA-identical sibling were included in a pilot study of nation with in vivo cyclosporin A induces a low rate of T cell subset depletion. Total depletion of CD4 + cells of GVHD with about 10% of graft failure after BMT using the marrow graft and partial depletion of CD8 + cells HLA-identical sibling donors. [16][17][18][19] Depletion of both CD4 + was performed by immunomagnetic separation. In and CD8 + cells leads to a low rate of aGVHD even in unorder to improve the engraftment rate, we infused a low related donor BMT, but leukemic relapse still remains a fixed number of CD8 + lymphocytes (0.25 × 10 6 /kg). All problem. 20 the patients were at high risk of developing acute graftIn animal models, it has been postulated that CD8 + cells versus-host disease (GVHD), with a recipient age of Ͼ30 may be important to ensure engraftment after BMT. 21 years, and/or donor sensitized by previous pregnancies Moreover, patients transplanted using a low fixed number or transfusions. All of them received cyclosporin A and of lymphocytes in the graft after physical depletion of T methotrexate post-BMT. No graft failure was observed.cells showed a stable and durable engraftment in the The grade III-IV GVHD rate was 16.6%, and the actumajority of cases, with an effective prevention of arial survival at 3 years is 81.8%. Immunological recovaGVHD. 22,23 ery showed persistent CD8 + HLA-DR + lymphocytosis 8We have developed a program of allogeneic bone marmonths after transplant. Relapses were not observed.row transplantation for patients with CML and with high This experience shows the importance of CD8 + cells to risk of aGVHD, using selective depletion of T cell subsets, ensure correct engraftment, decreasing the GVHD rate.by total immunomagnetic CD4 + depletion and partial CD8 + Keywords: T cell subset depletion; CD8 + lymphocytes; depletion. We infused a low fixed number of CD8 + cells GVHD prevention; graft failure with the graft to attempt an effective prevention of aGVHD, ensuring engraftment and without increasing the rate of leukemic relapses. We have previously reported 24,25 our initial experience Acute graft-versus-host disease (aGVHD) is an import...
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