Five year leukaemia-free survival of 72% and 77% for early stage acute and chronic myeloid leukaemia treated by HLA-identical sibling bone marrow transplantation

Background: HLA-identical sibling bone marrow transplantation is an accepted treatment for patients with acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML). We have recently reported improving results in HLA-identical sibling transplant over the ten year period 1981-1990. In this report we described the outcome in patients transplanted at St Vincent's Hospital, Sydney between 1989 and 1993. Aims: To determine the leukaemia-free survival, transplant-related mortality rate, and relapse rate for patients with AML or CML given HLA-identical sibling marrow transplants between 1989 and 1993. Methods: Sixty-two patients with AML or CML received high dose busulphan/cyclophos-phamide chemotherapy followed by infusion of T replete, HLA-identical sibling bone marrow. Cyclosporin/short methotrexate was utilised as prophylaxis for graft-versus-host disease, ganciclovir as prophylaxis for cytomegalovirus disease and cotrimoxazole as prophylaxis for Pneumocystis carinii pneumonia. Low dose intravenous heparin was used as prophylaxis for hepatic veno-occlusive disease. Results: The five year disease-free survival for patients with AML transplanted in first complete remission was 72% and for those with CML transplanted in first chronic phase was 77%. The relapse rate for AML transplanted in first complete remission was 15% and for CML in first chronic phase 0%. The transplant-related mortality for AML transplanted in first complete remission was 16% and for CML transplanted in first chronic phase 23%. In contrast, the disease-free survival, relapse rate and transplant-related mortality for patients with AML transplanted outside first complete remission and for CML transplanted beyond first chronic phase was 17%, 57% and 57% respectively. Conclusions: The outcome for patients transplanted for early AML or early CML continues to improve and exceeds that obtainable by conventional therapy. The salvage rate is so low for patients transplanted in later stages of AML or CML that all patients less than 55 years of age with these diseases, who have a HLA-identical sibling donor, should be offered bone marrow transplantation early in their disease course.     

Autologous haematopoietic stem cell transplants for autoimmune disease--feasibility and transplant-related mortality. Autoimmune Disease and Lymphoma Working Parties of the European Group for Blood and Marrow Transplantation, the European League Against Rheumatism and the International Stem Cell Project for Autoimmune Disease.

This ongoing multicentre prospective phase I/II trial enrolled 74 consecutive patients from 22 centres worldwide with severe autoimmune disease, 35 with rheumatological disorders, 31 with neurological, five with haematological and three with vasculitides. They were treated with autologous peripheral blood or bone marrow transplants according to predetermined criteria. Two patients died after mobilisation before transplant. Seventy-two patients were given 73 transplants, seven bone marrow, and 66 mobilised peripheral blood stem cell transplants. The graft was manipulated to remove T and/or B cells in 43 cases. All 73 transplants engrafted. Five patients died of transplant-related complications: two from bleeding, three from infections. Two patients died of progressive disease. The transplant-related mortality at 1 year of 9% (1-17%; 95% CI) is comparable to the transplant-related mortality of 6% (3-9%; 95% CI) in patients transplanted during the same period in Europe for non-Hodgkin's lymphoma in sensitive relapse (P = 0.39). Sixty patients are evaluable for response, 40 patients (65%) showed some improvement in their disease. Haematopoietic stem cell transplants are feasible for patients with severe refractory autoimmune disease. Transplant-related mortality is comparable to results in patients with non-Hodgkin's lymphoma in responsive relapse. Two-thirds of the patients show at least some response. These preliminary data are promising. Although associated with considerable risk, randomised trials comparing autologous stem cell transplants to conventional therapy are warranted.     

THE IMPACT OF LEUKEMIA STATUS AT THE TIME OF HLA-IDENTICAL SIBLING MARROW TRANSPLANTATION ON SUBSEQUENT COMPLICATION RATE AND SURVIVAL OF ADULTS WITH ACUTE LEUKEMIA

Between March 1981 and March 1985, 76 patients with acute leukemia were treated with cyclophosphamide (120 mg/kg), 12 or 14 Gy total body irradiation, and an HLA-identical sibling marrow transplant. Forty-seven patients had acute non-lymphoblastic leukemia (ANLL) and 29 had acute lymphoblastic leukemia (ALL). Forty-one were transplanted during first remission and 28 during or after first relapse of their disease. An additional six patients were transplanted because their leukemia was refractory to conventional cytotoxic chemotherapy, and one was transplanted as initial therapy. Actuarial 42 month survival for those transplanted during first remission was 47% and for those transplanted in first relapse or later it was 22% (p = 0.02). There was no difference in either group between those with ANLL and those with ALL. Two of the six patients with refractory leukemia are alive more than 22 and more than 15 months after the transplant. The incidence of acute graft-versus-host disease and interstitial pneumonitis was 90% and 39%, respectively, for the first remission group, and 96% and 37% for those transplanted in first relapse or later. There was no significant difference in transplant-related mortality between the two groups (29% and 43%, respectively). The leukemia recurrence rate, however, was 13% for those transplanted in first remission and 67% for those transplanted in first relapse or later (p = 0.0003). Thus, the major factor determining the incidence of leukemia recurrence and survival after transplant was the status of the leukemia at the time of transplantation. These findings indicate that adults with acute leukemia who have an HLA-identical sibling should be transplanted in first remission, and that transplant-related mortality must be reduced urgently. (Aust NZ J Med 1986; 16: 462–469.)     

Cord blood transplantation for children with acute leukaemia: a Eurocord registry analysis

OBJECTIVES: Report results of unrelated cord blood transplants collected by Eurocord Registry in children with acute leukemia. RESULTS: Children with AML: 95 children were analyzed. The two year leukemia free survival was 42% in patients transplanted in first remission, 50% in second remission and 21% in children not in remission. Children with poor prognostic cytogenetic features had the same survival compared to other patients. Children with ALL: 195 patients with ALL were analyzed. The two year leukemia free survival was 36% in patients transplanted in remission and 15% in patients transplanted in relapse. Results of unrelated cord blood transplants compared to unrelated bone marrow transplants in children with acute leukemia: 416 children with acute leukemia received a HLA matched unrelated bone marrow transplant and were compared to 99 children transplanted with an unrelated HLA mismatched cord blood. The long term outcome between these groups were comparable with delayed engraftment in cord blood transplant, more relapse in T cell depleted bone marrow transplant and more GVH in the unmanipulated bone marrow transplant resulting in similar 5 years leukemia free survival. CONCLUSION: These results show that use of unrelated cord blood transplant is an option in patients lacking an HLA identical sibling donor.     

CD34+ cell dose predicts relapse and survival after T-cell-depleted HLA-identical haematopoietic stem cell transplantation (HSCT) for haematological malignancies

Seventy-eight patients with haematological malignancies, received T-cell-depleted stem cell transplants and cyclosporin followed by delayed add-back of donor lymphocytes to prevent leukaemia relapse. The source of stem cells was bone marrow in 50 patients and granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood in 28 patients. In univariate analysis, only the CD34+ cell dose (but not the stem cell source or the T lymphocyte dose) and disease status were predictive for transplant-related mortality, relapse and survival. Patients receiving >/= 3 x 106 CD34+ cells/kg had an overall actuarial survival of 68% compared with 52%, 35% and 10%, respectively, for cell doses of 2-2.99, 1-1.99 and < 1 x 106/kg. Multivariate analysis of risk factors for relapse identified disease risk and CD34+ cell dose as the only factors. Relapse was 62.5% in 38 patients at high risk of relapse vs. 25% for 40 patients at intermediate or low risk. CD34+ cell doses of >/= 3 x 106/kg were associated with a 13.5% relapse vs. 48% for recipients of lower doses. This favourable effect of CD34+ cell dose on relapse was apparent in both high- and intermediate- plus low-risk groups. Our results support the potential benefit of a high stem cell dose in lowering transplant-related mortality (TRM) and in reducing relapse after allogeneic marrow or blood stem cell transplants.     

Unrelated volunteer bone marrow transplantation: initial experience at St Vincent's Hospital, Sydney

Background: Only 30% of patients with leukaemia have an HLA-compatible family member able to act as a marrow donor. The recent development of volunteer bone marrow donor registries has supplied HLA-matched donors for a number of such individuals. Aims: To define the problem and outcome of the first cohort of patients given HLA-matched unrelated volunteer bone marrow transplants at St Vincent's Hospital, Sydney. Methods: Post transplant outcome of patients with advanced leukaemia given HLA-identical unrelated donor marrow transplants was compared to that of patients transplanted concurrently from HLA-identical sibling donors, in terms of survival, leukaemia-free survival, incidence and severity of acute graft-versus-host disease (GVHD), duration of neutropenia, incidence of infection and duration of transplant hospitalisation. Results: Sixteen patients with advanced leukaemia and without a histocompatible family member donor received unrelated donor bone marrow transplants. Actuarial survival at two years post transplant was 30%. Actuarial survival of 23 recipients of HLA-identical sibling bone marrow transplants with advanced leukaemia transplanted during the same time period was 17% (not significant). Actuarial disease free survival at two years was 30% and 13% respectively. Three of five long term survivors of the unrelated transplants had chronic myeloid leukaemia in blastic transformation at the time of transplant; thus blastic transformation should not preclude consideration of unrelated marrow transplantation. Recipients of unrelated allografts had a higher incidence of acute GVHD which occurred earlier and with greater severity than in recipients of sibling allografts, a longer duration of post transplant neutropenia (24 days to reach 0.5 × 10⁹/L versus 19.5, p= 0.07), a higher frequency of infection in the first 100 days post transplant (p= 0.0004) and a longer duration of transplant hospitalisation (p= 0.04). Transplant-related complications were the commonest cause of death in the unrelated donor recipients, while leukaemic recurrence was the commonest single cause of death in the HLA-identical sibling recipients. Improvements are needed in prophylaxis of infection and in prevention and treatment of acute GVHD in recipients of unrelated donor transplants. Nevertheless, this modality provides curative treatment for patients with otherwise incurable haematological malignancies and should no longer be considered experimental. (Aust NZ J Med 1993; 23: 450–457.)     

Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation

Aplastic anemia is usually treated with immunosuppression or allogeneic transplant, depending on patient and disease characteristics. Syngeneic transplant offers a rare treatment opportunity with minimal transplant-related mortality, and offers an insight into disease mechanisms. We present here a retrospective analysis of all syngeneic transplants for aplastic anemia reported to the European Group for Blood and Marrow Transplantation. Between 1976 and 2009, 88 patients received 113 transplants. Most transplants (n=85) were preceded by a conditioning regimen, 22 of these including anti-thymocyte globulin. About half of transplants with data available (39 of 86) were followed by posttransplant immunosuppression. Graft source was bone marrow in the majority of cases (n=77). Transplant practice changed over time with more transplants with conditioning and anti-thymocyte globulin as well as peripheral blood stem cells performed in later years. Ten year overall survival was 93% with 5 transplant-related deaths. Graft failure occurred in 32% of transplants. Risk of graft failure was significantly increased in transplants without conditioning, and with bone marrow as graft source. Lack of posttransplant immunosuppression also showed a trend towards increased risk of graft failure, while anti-thymocyte globulin did not have an influence. In summary, syngeneic transplant is associated with a significant risk of graft failure when no conditioning is given, but has an excellent long-term outcome. Furthermore, our comparatively large series enables us to recommend the use of pre-transplant conditioning rather than not and possibly to prefer peripheral blood as a stem cell source.     

Matched-related donor transplantation for sickle cell disease: report from the Center for International Blood and Transplant Research

We report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)-matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso-occlusive crisis in 38% and 37% of patients respectively. The median age at transplantation was 10 years and 67% of patients had received >10 red blood cell transfusions before HCT. Twenty-seven percent of patients had a poor performance score at transplantation. Ninety-four percent received busulfan and cyclophosphamide-containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post-transplant period. Rates of acute and chronic graft-versus-host disease were 10% and 22% respectively. Sixty-four of 67 patients are alive with 5-year probabilities of disease-free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle-related events. This report confirms and extends earlier reports that HCT from HLA-matched related donors offers a very high survival rate, with few transplant-related complications and the elimination of sickle-related complications in the majority of patients who undergo this therapy.     

Risk factors for acute GVHD and survival after hematopoietic cell transplantation

Risk factors for acute GVHD (AGVHD), overall survival, and transplant-related mortality were evaluated in adults receiving allogeneic hematopoietic cell transplants (1999-2005) from HLA-identical sibling donors (SDs; n = 3191) or unrelated donors (URDs; n = 2370) and reported to the Center for International Blood and Marrow Transplant Research, Minneapolis, MN. To understand the impact of transplant regimen on AGVHD risk, 6 treatment categories were evaluated: (1) myeloablative conditioning (MA) with total body irradiation (TBI) + PBSCs, (2) MA + TBI + BM, (3) MA + nonTBI + PBSCs, (4) MA + nonTBI + BM, (5) reduced intensity conditioning (RIC) + PBSCs, and (6) RIC + BM. The cumulative incidences of grades B-D AGVHD were 39% (95% confidence interval [CI], 37%-41%) in the SD cohort and 59% (95% CI, 57%-61%) in the URD cohort. Patients receiving SD transplants with MA + nonTBI + BM and RIC + PBSCs had significantly lower risks of grades B-D AGVHD than patients in other treatment categories. Those receiving URD transplants with MA + TBI + BM, MA + nonTBI + BM, RIC + BM, or RIC + PBSCs had lower risks of grades B-D AGVHD than those in other treatment categories. The 5-year probabilities of survival were 46% (95% CI, 44%-49%) with SD transplants and 33% (95% CI, 31%-35%) with URD transplants. Conditioning intensity, TBI and graft source have a combined effect on risk of AGVHD that must be considered in deciding on a treatment strategy for individual patients.     

Allogeneic transplantation using peripheral blood stem cells

Over the past 9 years there has been a remarkable increase in the use of peripheral blood stem cells (PBSC) for allogeneic transplantation, primarily for matched sibling transplants but also increasingly for unrelated donor transplantation. In 1999 over 50% of all sibling transplants and over 25% of unrelated donor transplants reported to the European Group for Blood and Marrow Transplantation (EBMT) used PBSC. The major reason for this increasing use of PBSC relates to the rapid haemopoietic recovery seen which mirrors the advantages of using PBSC in autologous transplantation. This improvement in engraftment is a consequence of the larger number of stem cells that can be collected from G-CSF-mobilized peripheral blood compared to bone marrow. Evidence from randomized trials now shows a survival advantage for the use of PBSC in patients with advanced leukaemia. The reason for this improved survival appears primarily to relate to a reduced risk of transplant-related mortality and, possibly, a reduced risk of relapse, However, these randomized studies have also confirmed that there is an increased risk of chronic graft-versus-host disease associated with PBSC transplantation and further follow-up is required to determine the long-term impact on outcome.     

Factors affecting long-term outcome after allogeneic haematopoietic stem cell transplantation for acute myelogenous leukaemia: a retrospective study of 172 adult patients reported to the Austrian Stem Cell Transplantation Registry

Between 1982 and 2000, 172 patients with acute myelogenous leukaemia (AML) received haematopoietic stem cell transplants (SCT) from related (n = 132) or unrelated (n = 40) donors at four Austrian transplant centres and their results were reported to the Austrian Stem Cell Transplantation Registry. Conditioning for SCT consisted of cyclophosphamide and total body irradiation in 156 (91%) patients. Graft-versus-host disease (GVHD) prophylaxis was with standard cyclosporine and methotrexate in 95 (55%) patients. Median post-transplant follow-up was 5.6 years (range, 0.2--16.7). Multivariate analysis of transplant-related mortality (TRM) identified four variables associated with a lower risk: disease status of first complete remission (CR) at SCT, patient age of 45 years and younger, transplant performed during or after 1995, and lack of acute GVHD. Variables associated with significantly improved leukaemia-free survival were: bone marrow as the stem cell source, disease status of first CR at SCT, and occurrence of chronic GVHD. In multivariate analysis, transplantation performed during or after 1995, first CR at SCT, occurrence of limited chronic GVHD and lack of acute GVHD grades III to IV were associated with increased overall survival. Based on these analyses, options for the improvement of results obtained with allogeneic SCT in patients with AML could be defined.     

Transplantation of fetal liver of different ages in the rat

Summary This study investigates the effect of fetal liver transplantation in reconstituting hemopoiesis in supralethally irradiated rats. Different cell doses of fetuses at the embryonic age of 15 and 18 days were compared to equivalent cell doses of adult bone marrow cells. Although the frequency of engraftment ranged between 75 and 100% in all the groups of animals studied, the survival rate at 30 days after TBI did not show any significant difference between the fetal liver and the bone marrow treated recipients. The bone marrow transplants performed in littermate rats almost doubled the percentage of survivors at 30 days and showed a cell dose relationship suggesting that, in the closed colony of random-bred rats used, the mortality after bone marrow and fetal liver transplants was mainly due to graft-versus-host-disease. Antibiotic prophylaxis and treatment during the experiment did not modify the results in a separate group of fetal liver and bone marrow transplanted rats. In the rat model system used in this set of experiments fetal liver did not reveal any advantage over bone marrow transplantation.Supported by CNR N 80.00486 Rome, Italy, and Stiftung Volkswagenwerk Hannover, Federal Republic of Germany     

Allogeneic bone marrow transplantation in aggressive non-Hodgkin's lymphoma (excluding Burkitt and lymphoblastic lymphoma): a series of 73 patients from the SFGM database

The place of allogeneic bone marrow transplantation (BMT) in the treatment of aggressive non-Hodgkin's lymphoma (NHL) remains controversial. We conducted a retrospective study of French experience in allografting NHL between 1984 and 1994. To improve the homogeneity of the study population, cases of low-grade, Burkitt and lymphoblastic NHL were excluded. 73 patients were included in the analysis. Median age at transplantation was 35 years (range 9-61 years); 64 patients were in stage IV and 45 had bone marrow involvement at diagnosis. At the time of transplantation, 46 patients had sensitive disease (25 in complete remission; CR). The overall survival (OS) and progression-free survival (PFS) rates were 41% and 40% respectively at 5 years (median follow-up of survivors 90 months). The probability of disease progression was 30% at 5 years, and only one relapse occurred after 15 months. 32 patients died of transplantation-related complications. In multivariate analysis, pretransplant complete remission was the main factor associated with longer survival (OS at 60 months of 76% among the 25 patients in CR at transplant and of 23% among the 48 patients not in CR at transplant). Neither acute nor chronic graft-versus-host disease (GvHD) influenced the relapse rate. In conclusion, in this high-risk population the overall results of allogeneic BMT were encouraging, despite a high transplant-related mortality rate. We believe this procedure should be studied further in prospective controlled trials.     

The impact of early CD4+ lymphocyte recovery on the outcome of patients who undergo allogeneic bone marrow or peripheral blood stem cell transplantation

Background

Different factors influence the clinical outcome of allogeneic transplants, the foremost being good immune recovery.

Materials and methods

The purpose of this study was to evaluate the influence of different factors, such as stem cell source, type of donor, conditioning regimen and acute graft-versus-host disease, on early lymphocyte recovery after transplantation. We then analyzed the impact of early CD4+ cell count on overall survival, transplant-related mortality and disease-related mortality.

Results

Univariate analysis with Spearman’s rho showed a significant correlation between early CD4+ cell recovery and overall survival, transplant-related mortality, stem cell source and type of donor. In multivariate analysis CD4+ cell count was significantly associated with (i) stem cell source, being higher in patients whose haematopoietic progenitor cells were obtained by apheresis than in those whose source of grafted cells was bone marrow, and (ii) type of donor, being higher in patients transplanted from sibling donors than in those whose graft was from an alternative donor. The ROC curve of CD4+ cell count indicated that a cut-off of 115 CD4+ cells/mL could differentiate groups with different outcomes. At 2 years follow-up, patients achieving this CD4+ cell count had significantly lower cumulative transplant-related mortality compared to patients who did not have this count (10%±4% versus 40%±8%, p=0.0026). At the 5-year follow-up, the overall survival rates were 77.5%±0.6% and 36%±7% (p=0.000) in patients with a CD4+ cell count ≥115/mL and in patients with CD4+ cell count ≤ 115/mL, respectively.

Conclusion

Early CD4+ cell recovery after allogeneic transplantation has a relevant impact on overall survival and transplant-related mortality and is influenced by two factors: stem cell source and type of donor.     

Current status of allogeneic bone marrow transplantation in acquired aplastic anemia

Bone marrow transplantation is an effective therapy for aplastic anemia. Infusion of allogeneic hematopoietic stem cells after high-dose immune suppression restores normal hematopoiesis in most patients and long-term follow-up has confirmed the durability of donor hematopoiesis. However, success of this approach is limited by transplant-related complications, such as graft failure, graft-versus-host disease, and various organ toxicities. Long-term survival rates range from less than 40% to more than 90% in reported series. These rates have improved over the past 20 years due to significant reductions in graft-versus-host disease, interstitial pneumonitis, and early transplant-related mortality. Most long-term survivors have excellent performance status. Late effects such as cataracts, thyroid disorders, joint problems, and therapy-related cancers are observed, especially in patients who received radiation for pretransplant conditioning. Results are best in young patients transplanted with bone marrow from a human leukocyte antigen (HLA)-identical sibling; early transplantation is appropriate in this group. For older patients or those without an HLA-identical related donor, transplants are better reserved for those who fail to respond to immunosuppressive therapy.     

Feasibility and recent improvement of autologous stem cell transplantation for acute myelocytic leukaemia in patients over 60 years of age: importance of the source of stem cells

A total of 193 patients with acute myelocytic leukaemia (AML) [147 in first complete remission (CR1)], ranging from 60 years to 75 years of age (median 63 years), were autografted between January 1984 and December 1998. The source of stem cells was peripheral blood (PB) in 128 patients, bone marrow in 51 patients and a combination of both in 14 patients. Total body irradiation (TBI) was used in 34 cases. Ninety-seven per cent of patients had successful engraftment of neutrophils on day 15 (range days 7-71) and of platelets on day 30 (range days 9-894). In patients autografted in CR1, the transplant-related mortality (TRM) was 15 +/- 4%, the relapse incidence (RI) was 58 +/- 5%, the leukaemia-free survival (LFS) was 36 +/- 5% and the overall survival was 47 +/- 5% at 3 years. The source and dose of stem cells were studied in particular; in patients transplanted in CR1, the RI was 44 +/- 11% in those receiving marrow compared with 63 +/- 6% in those receiving PB (P = 0.04). Patients autografted in CR1 who received higher granulocyte-macrophage colony-forming units (CFU-GM) doses (above the median) had a lower RI (47 +/- 11% vs. 79 +/- 9%, P = 0.009). There was a significant improvement in patients transplanted after March 1996; for those in CR1, the RI was 41 +/- 8% vs. 65 +/- 6% (P = 0.01), the LFS was 53 +/- 8% vs. 28 +/- 5% (P = 0.01) and the overall survival was 72 +/- 7% vs. 36 +/- 6% (P = 0.02). By multivariate analyses, significant factors for the outcome were the date of transplant with recent improvement and the source of stem cells, with a lower RI for marrow. Autologous stem cell transplantation (ASCT) is a potential therapeutic approach in patients with AML over 60 years of age; results have improved recently.     

European Group for Blood and Marrow Transplantation Registry studies in multiple myeloma

The European Group for Blood and Marrow Transplantation (EBMT) Myeloma Registry, established in 1987, contains data on 1,368 allogeneic and more than 8,000 autologous stem cell transplants performed since 1983. Among autologous transplant patients, the median survival after transplantation is 50 months, and the actuarial survival at 10 years is 30%, with a plateau appearing at about 8 years. Factors of importance for a more favorable prognosis are lower age, response to chemotherapy, only one course of primary chemotherapy, stage I or II disease, and low beta(2)-microglobulin at diagnosis. Beneficial procedural factors associated with better outcome are a preparative regimen without total body irradiation (TBI), posttransplant interferon alfa maintenance treatment, and possibly tandem transplantation. In vitro graft purging, using CD34(+) selection, does not have any impact on survival. A case-matched analysis comparing autologous and allogeneic transplantation demonstrated significantly better survival in the former group, with median posttransplant survival times of 36 months and 18 months in the autologous and allogeneic groups, respectively. This result was in turn due to a markedly lower incidence of transplant-related death among the autotransplant patients: 13%, versus 41% for the allogeneic group. However, recent data on allogeneic transplants performed from 1994 to 1998 has demonstrated a decrease in treatment-mortality to 30%, and this has resulted in a prolongation of survival; in this analysis, the results are similar irrespective of the type of graft used, allogeneic bone marrow or blood stem cells. In a small case-matched analysis, transplantation with an identical twin donor was superior to both allogeneic and autologous transplantation with respect to survival and freedom from progression.     

Allo-SCT for multiple myeloma: a review of outcomes at a single transplant center

Allogeneic stem cell transplant for multiple myeloma (MM) is one treatment associated with long-term disease-free survival. The high incidence of treatment-related mortality and relapses, however, are important reasons for controversy about the role of allografting in the management of MM. We reviewed our results of allografting for MM spanning a period of 34 years in order to better define long-term outcomes and identify areas of progress as well as areas requiring improvement. A total of 278 patients received allogeneic marrow or PBSCs after high-dose myeloablative (N=144) or reduced intensity, non-myeloablative (N=134) regimens. In multivariable analysis, adjusting for differences in patient groups, reduced intensity/non-myeloablative transplants were associated with significantly less acute GVHD, lower transplant mortality, better PFS and overall survival. There were no significant differences in relapse, progression or chronic GVHD, when adjusted. In multivariable analysis of patients receiving only non-myeloablative transplants, decreased overall survival and PFS were associated with relapse after a prior autograft and a β2 microglobulin >4.0. Transplant mortality was reduced and only influenced by a prior tandem autograft.     

Comparison of outcome following allogeneic bone marrow transplantation with cyclophosphamide-total body irradiation versus busulphan-cyclophosphamide conditioning regimens for acute myelogenous leukaemia in first remission

We evaluated transplant-related mortality (TRM), leukaemia relapse, leukaemia-free survival (LFS) and overall survival (OS) in patients receiving busulphan and cyclophosphamide (BuCy) or cyclophosphamide and total body irradiation (CyTBI) prior to allogeneic bone marrow transplantation (BMT) for acute myelogenous leukaemia (AML) in first remission. Outcomes of 381 human leucocyte antigen (HLA)-matched sibling transplants using BuCy were compared with 200 transplants using CyTBI performed between 1988 and 1996. The incidence of hepatic veno-occlusive disease was higher with BuCy (13%) than with CyTBI (6%) (P = 0.009). Risks of acute and chronic GVHD were similar. In multivariate analysis, relapse risk was higher in the BuCy group [relative risk (RR) = 1.72; 95% confidence interval (CI), 1.05-2.81; P = 0.031]. Eleven of 373 evaluable patients in the BuCy group had a central nervous system relapse in contrast to none of 194 evaluable patients in the CyTBI group (P = 0.016). There were no differences in TRM, LFS and OS. CyTBI conditioning may lower relapse risk but produces comparable TRM, LFS and OS to BuCy for HLA-matched sibling transplantation in first remission AML.     

Increased risk of extensive chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplantation using unrelated donors

The long-term follow-up of a study including 214 patients receiving either peripheral blood stem cells (PBSCs) or bone marrow (BM) from an HLA-A, -B, and -DR-compatible unrelated donor is presented. Median follow-up was 4.4 (2.3-7.3) and 5.0 (0.7-8.4) years in the 2 groups, respectively. Cumulative incidence of overall chronic graft-versus-host disease (GVHD) was similar in the 2 groups (78% vs 71%), while extensive chronic GVHD was significantly more common in the PBSC group compared with the BM group (39% vs 24%, P = .03). The 5-year transplant-related mortality (TRM) was 37% in the PBSC group and 35% in the BM controls (P = .7), and overall survival was 42% in both groups. The relapse incidences were 26% and 27% in the 2 groups, respectively, resulting in a disease-free survival of 41% in both groups. In conclusion, PBSCs from HLA-compatible unrelated donors results in similar outcome compared to BM but implies an increased risk for extensive chronic GVHD.