Factors influencing outcome and incidence of long-term complications in children who underwent autologous stem cell transplantation for acute myeloid leukemia in first complete remission

To evaluate factors influencing outcome and incidence of long-term complications, we analyzed, in a retrospective, multicenter study, 387 children who underwent autologous hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) in first complete remission (CR). Median follow-up time from transplantation was 60 months. Transplantation of bone marrow cells was performed in 318 children, whereas in 60 patients peripheral blood progenitor cells (PBPCs) were used. In multivariate analysis, we investigated the variables influencing probability of hematopoietic recovery, transplantation-related mortality (TRM), relapse, and leukemia-free survival (LFS). We found that use of PBPCs as stem cell sources and use of BCNU (N,N-bis[2-chloroethyl]-N-nitrosourea), amsacrine, VP-16, and cytosine arabinoside (BAVC) as a preparative regimen were associated with faster neutrophil recovery. Infusion of PBPCs, young age of patients, use of BAVCs, and absence of marrow purging predicted an accelerated platelet reconstitution. The 5-year Kaplan-Meier estimates of TRM, relapse, and LFS were 3% +/- 1%, 39% +/- 3% and 60% +/- 3%, respectively. Relapse probability was increased in children given the BAVC regimen, and it was decreased after in vitro purging of hematopoietic progenitors and in children with a French-American-British classification of M3 and a time interval of 170 days or more between CR and HSCT. These 2 latter variables favorably influenced the probability of LFS, which was, by contrast, reduced with the BAVC regimen. Thirty-three percent of patients surviving more than 18 months experienced at least one late sequela; use of total body irradiation was the only predictive factor. The results obtained in this analysis can be of help in designing prospective studies of autologous HSCT in children with AML in first CR.     

Long-term outcome of allogeneic PBSC transplantation in pediatric patients with hematological malignancies: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) and the Spanish Group for Allogeneic Peripheral Blood Transplantation (GETH)

We analyzed the clinical outcome in 90 children undergoing allogeneic PBSC transplantation from HLA-identical relative for leukemia. GvHD prophylaxis was CsA+ methotrexate in 50 and CsA+/-steroids in 40. Median CD34+ cells infused were 6 x 10(6)/kg (range, 1.4-32). Median follow-up was 60 months (range, 6-115). CI of transplant-related mortality (TRM) was 18.4+/-4%. On multivariate analysis, high Lansky score (>80) at transplantation was associated with lower TRM (HR, 0.9; P<0.0002). Relapse incidence (RI) was 33.6+/-6%. On multivariate analysis, high Lansky score at transplantation and cGvHD were associated with lower RI (HR, 0.04; P<0.0005 and HR, 0.23; P<0.03, respectively). Disease-free survival (DFS) was 57.8+/-5%. Disease status at transplantation (HR, 0.33; P<0.02), steroid treatment at day +90 (HR, 5.61; P<0.005) and cGvHD (HR, 0.23; P<0.005) had a significant impact on DFS in multivariate analysis. CI of cGvHD was 63.7+/-7%. Patients with cGvHD had better DFS (65+/-5%) because of lower RI (15.7+/-6%) and similar TRM (27.4+/-4%). These data suggest acceptable long-term outcomes after allogeneic PBSC transplantation in children despite the high incidence of cGvHD. These patients had a lower risk of relapse and a better DFS.     

Autologous hematopoietic stem cell transplantation for adults with acute myeloid leukemia in complete remission: the Edouard Herriot Hospital experience

We retrospectively assess the long-term outcome and determined prognostic factors correlated with outcomes in adults with acute myeloid leukemia (AML) undergoing autologous hematopoietic stem cell transplantation (HSCT) in our institution over a 19-year period. A total of 78 adults who received autologous HSCT for AML in first complete remission (CR) and of 21 adults in further CR were included in the study. Bone marrow (n = 14) or peripheral blood stem cells (PBSC) (n = 85) transplantation was performed at a median of 2.9 months from CR. Hematologic recovery was significantly reduced in the PBSC group. Five-year cumulative incidences of relapse were 56 and 49%, respectively. Corresponding 5-year probabilities of event-free survival (EFS) were 33 and 35%, while those of overall survival (OS) were 38 and 49%, respectively. In multivariate analyses, cytogenetics was the main prognostic factor for outcome. Treatment-related mortality (TRM) was of 15% at 5 years, but higher in females as compared to males (p = 0.04). We confirmed that long-term EFS can be achieved after autologous HSCT in adult patients with AML. Results in adults who experience a relapse after conventional chemotherapy support the use of autologous HSCT as salvage therapy if such patients achieve a subsequent CR.     

Allogeneic or autologous stem cell transplantation (SCT) for relapsed and refractory Hodgkin's disease and non-Hodgkin's lymphoma: a single-centre experience

PURPOSE OF THE STUDY: The aim of the study was to evaluate which patient might benefit most from allogeneic stem cell transplantation (SCT) in the treatment of relapsed and/or refractory lymphoma. PATIENTS AND METHODS: Thirty-eight consecutive lymphoma patients receiving either autologous (n = 24) or allogeneic (n = 14) stem cell grafts at our institution from 1986 to 1998 were retrospectively analysed regarding overall survival (OS), disease-free survival (DFS), transplant-related mortality (TRM), and relapse incidence (RI). Uni- and multivariate analyses were performed to identify patient characteristics predictive for outcome after SCT. RESULTS: The probabilities of OS, DFS, TRM, and relapse were 57%, 51%, 29%, and 30% following autologous and 43%, 43%, 29%, and 38% following allogeneic SCT. Disease status (sensitive versus refractory) and the time interval between diagnosis and SCT were the most powerful predictive parameters for OS and TRM, whereas elevated serum LDH levels were signifcant in determining relapse. CONCLUSIONS: In patients with elevated serum LDH levels and bone marrow involvement at the time of transplantation allogeneic was superior to autologous SCT and resulted in better outcome due to a lower relapse incidence strongly suggesting the existence of a graft-versus-lymphoma effect.     

Hematopoietic stem cell transplantation for adults with acute promyelocytic leukemia in the ATRA era: a survey of the European Cooperative Group for Blood and Marrow Transplantation

We performed a survey of the European Cooperative Group for Blood and Marrow Transplantation to analyze the outcome of 625 acute promyelocytic leukemia (APL) patients transplanted with auto- or allogeneic-hematopoietic stem cell transplantation (autoHSCT, alloHSCT) after 1993, in first (CR1) or in second complete remission (CR2). Leukemia-free survival (LFS) at 5 years in CR1 was 69% for 149 patients autografted and 68% for 144 patients allografted, whereas in CR2, LFS was 51% in 195 autoHSCT and 59% in 137 alloHSCT recipients, respectively. In the group of autoHSCT for CR1 (n=149), higher relapse incidence (RI) was associated with shorter time from diagnosis to transplant (<7.6 months); transplant-related mortality (TRM) was increased in older patients (>47 years), whereas for CR2, longer time from diagnosis to transplant (>18 months) was associated with increased LFS and decreased RI. In the alloHSCT group for CR1 (n=144), age (<33 years) was associated with increased LFS and decreased TRM and for CR2 (n=137), the use of mobilized peripheral blood stem cells was associated with decreased TRM. Female recipient, a female donor to male recipient and transplants performed before 1997 were associated with decreased RI. In conclusion, HSCT still appears to have a role in APL, especially for patients in CR2.     

A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia

We retrospectively compared the outcome in patients in the EBMT database transplanted for acute leukaemia from January 1987 to January 1994 who received busulphan and cyclophosphamide (BU/CY) as a pretransplant regimen versus those who received cyclophosphamide and total-body irradiation (CY/TBI). The patients were matched for type of transplant (autologous bone marrow transplantation (ABMT) versus allogeneic (BMT)), diagnosis (acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML)), status (early (first complete remission, CR-1) versus intermediate (second or later remission, first relapse)), age, FAB classification for AML, prevention of graft-versus-host disease and year of transplantation. In ABMT recipients (matched paired 530 × 2) with ALL CR-1, AML CR-1 and AML intermediate disease, transplant-related mortalities (TRM), relapse incidence (RI) and leukaemia-free survival (LFS) did not differ significantly in patients treated with BU/CY or CY/TBI. However, in ABMT recipients with ALL intermediate disease, the probability of relapse was 82 ± 5% (±95% confidence interval) in the BU/CY group compared to 62 ± 6% in the CY/TBI group (P = 0.002) and the 2-year leukaemia-free survival 14 ± 4% and 34 ± 6%, respectively (P = 0.002). In BMT recipients of bone marrow from HLA-identical siblings (matched paired 391 × 2), the TRM, RI and LFS did not differ significantly between the two treatments in all groups. In particular, the 2-year LFS in patients with AML CR-1 was 64 ± 3% in those treated with BU/CY (n = 237) compared to 66 ± 3% in those given CY/TBI (n = 237). In all groups the findings were confirmed in a multivariate analysis of prognostic factors. Veno-occlusive disease (VOD) of the liver (P < 0.05) and haemorrhagic cystitis (P < 0.001) was more common in the BU/CY group compared to the CY/TBI group for ABMT and BMT patients. In conclusion, BU/CY and CY/TBI as pretransplant regimens gave similar results in all situations, except ABMT for ALL intermediate stages with more than 2 years from diagnosis to transplantation, where a lower RI and a higher LFS were associated with CY/TBI.     

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.     

Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Société Française de Greffe de Moelle (SFGM)

To assess the place of allogeneic hematopoietic stem cell transplantation (HSCT) in the advanced stage of acute myeloid leukemia (AML), we retrospectively analyzed 379 consecutive patients who underwent allogeneic HSCT for advanced AML. The median follow-up of the entire cohort was 7.5 years. Sixty-nine patients (18%) were transplanted with primary resistant disease. Three hundred and ten (82%) were relapsed patients, 94 (30%) of whom were in untreated relapse, 67 (22%) in refractory relapse and 149 (48%) in 2nd or 3rd complete remission at time of transplantation. The 5-year probabilities of overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM) were 22 +/- 4%, 20 +/- 4%, 45 +/- 6%, respectively. In multivariate analysis, we demonstrated the favorable impact on OS, DFS and TRM of two factors over which we have no control (age <15 years, complete remission achievement) and three factors over which we have some control (female donor, acute and chronic graft-versus-host disease). The results of this study suggest that the graft-versus-leukemia effect is important in advanced AML and that new HSCT modalities are needed for some patients with this indication.     

Hematopoietic stem cell transplantation for de novo acute megakaryocytic leukemia in first complete remission: a retrospective study of the European Group for Blood and Marrow Transplantation (EBMT)

Acute megakaryoblastic leukemia (M7 AML) is a highly aggressive disease. We evaluated outcomes in 57 children (11 with Down syndrome) and 69 adults with M7 AML after first complete remission (CR1) following autologous or HLA-identical allogeneic transplantation. Characteristics of the recipients of autologous transplants (38 children, 37 adults) were, respectively: median age, 1.7 and 46 years; non-total body irradiation (non-TBI) conditioning regimen, 97% and 70%; bone marrow as stem cell source, 74% and 43%. Characteristics of the recipients of allogeneic transplants (19 children, 32 adults) were, respectively: median age, 2.8 and 37 years; non-TBI regimen, 63% and 42%; bone marrow as stem cell source, 95% and 69%. Autologous transplantation benefited children more; the relapse rate was high in adults. Results for autologous transplantation were (children and adults, respectively): engraftment, 90% and 100%; 3-year treatment-related mortality (TRM) rate, 3% and 8%; relapse rate, 45% and 64%; leukemia-free survival (LFS) rate, 52% and 27%; overall survival (OS) rate, 61% and 30%. After allogeneic transplantation, TRM was fairly low in children and adults, and relapse rates were lower than after autologous transplantation. Results for allogeneic transplantation were, respectively: engraftment, 95% and 90%; TRM, 0% and 26%; relapse rate, 34% and 28%; LFS, 66% and 46%; OS, 82% and 43%). We conclude that M7 AML patients in CR1 (except children with Down syndrome, who already have better outcomes) can benefit from transplantation.     

Conventional versus reduced-intensity conditioning regimen for allogeneic stem cell transplantation in patients with hematological malignancies

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA)-compatible sibling donors is a potential curative treatment for hematological and non-hematological malignancies. Nevertheless, high mortality rates may be associated with this therapy, especially in older patients, those with other comorbidities or who receive a second HSCT. PATIENTS AND METHODS: We analyzed the factors associated with transplant-related mortality (TRM) and overall survival in 157 consecutive adult patients (104 males and 53 females) who received a HSCT [29 bone marrow (BM) transplantation and 128 peripheral blood (PB) transplantation] from a HLA-identical sibling between January 1995 and March 2002 in our institution. One hundred patients received a standard conditioning prior to HSCT (STAND) and 57 patients received a reduced-intensity conditioning (RIC) HSCT. Fifty-eight patients were in an early phase at transplant and 99 in a non-early phase. Median age was 46 yr (16-66), and 90 patients (57%) were >45 yr of age. RESULTS: Patients in the RIC group were older than those in the STAND group, and had a higher proportion of non-early disease phases including a prior autologous HSCT in 39%. Median follow-up for survivors was 28 and 15 months in the STAND and RIC groups (P < 0,001), respectively. Cumulative incidence of TRM at 2 yr was 30% [95% confidence interval (CI) 22-41%] for the STAND group and 22% (95% CI 13-37%) for the RIC group [non-significant (NS)]. Factors associated with a higher TRM in multivariate analysis were: STAND vs. RIC conditioning regimen [relative risk (RR) 5.4; 95% CI 2.3-12.8; P < 0.001]; age > or =45 yr vs. <45 yr (RR 5; 95% CI 2.4-10.8, P < 0.001); second vs. first HSCT (RR 2.8, 95% CI 1.3-6.3, P = 0.01) and non-T-cell-depleted vs. T-cell-depleted graft (RR 2.7, 95% CI 1.3-5.8, P = 0.009). Overall survival (OS) at 2 yr was 52.5 +/- 10.4% for STAND group and 59 +/- 16.8% in RIC group. Factors associated with poorer OS in multivariate analysis were: STAND vs. RIC conditioning regimen (RR 3.4, 95% CI 1.7-6.9, P = 0.001); age > or =45 vs <45 yr (RR 2.5, 95% CI 1.4-4.5, P = 0.002) and diagnosis [other than chronic myeloid leukemia (CML) vs. CML] (RR 2.6, 95% CI 1.2-5.7 P = 0.02). CONCLUSIONS: Our results indicate that the introduction of RIC allogeneic HSCT for patients at high risk for TRM (advanced age, prior HSCT and non-T-cell depletion) leads to a reduction in the TRM and improvement in the OS.     

Autotransplantation versus HLA-matched unrelated donor transplantation for acute myeloid leukaemia: a retrospective analysis from the Center for International Blood and Marrow Transplant Research

Most acute myeloid leukaemia (AML) patients lack human leucocyte antigen-identical sibling donors for transplantation. Autotransplants and unrelated donor (URD) transplants are therapeutic options. To compare autologous versus URD transplantation for AML in first (CR1) or second complete remission (CR2), we studied the outcomes of 668 autotransplants were compared with 476 URD transplants reported to the Center for International Blood and Marrow Transplant Research. Proportional hazards regression adjusted for differences in prognostic variables. In multivariate analyses transplant-related mortality (TRM) was significantly higher and relapse lower with URD transplantation. Adjusted 3-year survival probabilities were: in CR1 57 (53-61)% with autotransplants and 44 (37-51)% URD (P = 0.002), in CR2 46 (39-53)% and 33 (28-38)% respectively (P = 0.006). Adjusted 3-year leukaemia-free survival (LFS) probabilities were: CR1 53 (48-57)% with autotransplants and 43 (36-50)% with URD (P = 0.021), CR2 39 (32-46)% and 33 (27-38)% respectively (P = 0.169). Both autologous and URD transplantation produced prolonged LFS. High TRM offsets the superior antileukaemia effect of URD transplantation. This retrospective, observational database study showed that autotransplantation, in general, offered higher 3-year survival for AML patients in CR1 and CR2. Cytogenetics, however, were known in only two-thirds of patients and treatment bias cannot be eliminated.     

Hematopoietic stem cell transplantation in Lebanon: first comprehensive report

Hematopoietic SCT (HSCT) has become a curative therapeutic strategy for several malignant and nonmalignant diseases. We report the comprehensive results of the first 10 years of experience in HSCT from the two major BMT units in Lebanon: Makassed University Hospital and the American University of Beirut Medical Center. The median and the 5-year overall survival (OS) were 97 months and 58%, respectively, for the 84 patients who received allogeneic HSCT, and 60 months and 50%, respectively, for the 228 patients who received autologous BMT. The results for myeloablative allogeneic transplantation were as follows: AML (n=28, 5-year OS 58%, 5-year disease-free survival (DFS) 48%), CML (n=9, 5-year OS 66%, 5-year DFS 52%), ALL (n=13, 2-year OS 10%, 2-year DFS 10%), thalassemia (n=10, 5-year transfusion-free survival 67%). The results for autologous HSCT were as follows: diffuse large B-cell lymphoma (DLBCL) in relapse (n=37, 5-year OS 68%, 5-year progression-free survival (PFS) 65%), Hodgkin's lymphoma (n=55, 5-year OS 55%, 5-year PFS 36%), and first-line multiple myeloma (n=71, 5-year OS 53%, 5-year PFS 24%). For allogeneic transplanted patients, the cumulative TRM was 23% and the incidence of acute GVHD was 23%. For autografted patients, TRM was 2.6%. These results indicate that despite the relatively low socioeconomic status of the Lebanese population, both allogeneic and autologous HSCT are feasible with outcomes similar to developed countries.     

Delaying haematopoietic stem cell transplantation in children with viral respiratory infections reduces transplant-related mortality

Viral respiratory infections (VRIs) contribute to the morbidity and transplant-related mortality (TRM) after allogeneic haematopoietic stem cell transplantation (HSCT) and strategies to prevent and treat VRIs are warranted. We monitored VRIs before and after transplant in children undergoing allogeneic HSCT with nasopharyngeal aspirates (NPA) and assessed the impact on clinical outcome. Between 2007 and 2017, 585 children underwent 620 allogeneic HSCT procedures. Out of 75 patients with a positive NPA screen (12%), transplant was delayed in 25 cases (33%), while 53 children started conditioning with a VRI. Patients undergoing HSCT with a positive NPA screen had a significantly lower overall survival (54% vs. 79%) and increased TRM (26% vs. 7%) compared to patients with a negative NPA. Patients with a positive NPA who delayed transplant and cleared the virus before conditioning had improved overall survival (90%) and lower TRM (5%). Pre-HSCT positive NPA was the only significant risk factor for progression to a lower respiratory tract infection and was a major risk factor for TRM. Transplant delay, whenever feasible, in case of a positive NPA screen for VRIs can positively impact on survival of children undergoing HSCT.     

Graft-versus-host disease and outcome in HLA-identical sibling transplantations for chronic myeloid leukemia

Graft-versus-host disease in its acute (aGvHD) or chronic form (cGvHD) remains the most important posttransplantation factor influencing outcome after allogeneic hematopoietic stem cell transplantation (HSCT). It increases transplantation-related mortality (TRM) but reduces risk of relapse. The net effect of these 2 discordant effects determines survival. In view of current interests to exploit graft-versus-leukemia (GVL) effects, we analyzed 4174 HLA-identical sibling transplantations for chronic myeloid leukemia in first chronic phase, depending on the presence or absence and severity of GvHD with a landmark analysis. During the first 100 days, only aGvHD grades III and IV had an impact on TRM. During the time period day 100 to 3 years increasing severity of aGvHD is associated with increased TRM and decreased relapse incidence (RI) with hazard ratios (HRs) for TRM as follows: grade 0, HR = 1.0; grade I, HR = 1.52 (1.19-1.96); grade II, HR = 2.48 (1.95-3.14); grade III, HR = 5.76 (4.44-7.48); grade IV, HR = 14.7 (10.9-19.9) and likewise for RI: grade I versus 0, HR = 0.94 (0.76-1.16); grade II, HR = 0.60 (0.46-0.77); grade III, HR = 0.48 (0.29-0.81); grade IV, HR = 0.14 (0.02-0.99). Beyond 3 years, TRM and RI are determined by cGvHD. Limited cGvHD reduces RI to the same extent as extensive cGvHD but has no impact on TRM and, hence, results in best survival with an HR = 0.48 (0.32-0.71). aGvHD grade I has the highest likelihood of subsequent limited cGvHD, which results in cumulative incidence estimates of survival at 10 years being best for patients with initial aGvHD grade I: survival at 10 years grade 0 = 59%, I = 63%, II = 56%, III = 26%, IV = not applicable. These data clarify the role of GvHD in posttransplantation outcome. Considerations for long-term outcome are essential when short-term data of interventions on GvHD are analyzed.     

Effect of acute and chronic GVHD on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma

We evaluated the effect of acute and chronic GVHD on relapse and survival after allogeneic hematopoietic SCT (HSCT) for multiple myeloma using non-myeloablative conditioning (NMA) and reduced-intensity conditioning (RIC). The outcomes of 177 HLA-identical sibling HSCT recipients between 1997 and 2005, following NMA (n=98) or RIC (n=79) were analyzed. In 105 patients, autografting was followed by planned NMA/RIC allogeneic transplantation. The impact of GVHD was assessed as a time-dependent covariate using Cox models. The incidence of acute GVHD (aGVHD; grades I-IV) was 42% (95% confidence interval (CI), 35-49%) and of chronic GVHD (cGVHD) at 5 years was 59% (95% CI, 49-69%), with 70% developing extensive cGVHD. In multivariate analysis, aGVHD (≥ grade I) was associated with an increased risk of TRM (relative risk (RR)=2.42, P=0.016), whereas limited cGVHD significantly decreased the risk of myeloma relapse (RR=0.35, P=0.035) and was associated with superior EFS (RR=0.40, P=0.027). aGVHD had a detrimental effect on survival, especially in those receiving autologous followed by allogeneic HSCT (RR=3.52, P=0.001). The reduction in relapse risk associated with cGVHD is consistent with a beneficial graft-vs-myeloma effect, but this did not translate into a survival advantage.     

Outcome of 5651 hematopoietic stem cell transplants for hematological malignancies carried out in Europe in 1993: a reliability study of the registry

Outcome results of observational databases are frequently criticized as relying on incomplete information from incomplete patient populations. Few data are available to dispute these arguments of selection bias. The European Group for Blood and Marrow transplantation (EBMT) decided to address this question by evaluating the hematopoietic stem cell transplants performed in 1993. A comprehensive survey was launched in an effort to collect informations on all transplants for hematological malignancies performed throughout Europe during the year 1993. The main goals of this effort were to compare the group of spontaneously reported patients with the group of retrospectively solicited patients, and to give an accurate estimate of the outcome of all patients. For the year 1993, the annual EBMT activity survey indicated 6336 transplants performed for hematological malignancies in Europe. A total of 5651 transplants could be analyzed; 2595 were reported spontaneously by the teams (group A) and 3056 were retrieved on solicitation (group B). Patients and transplant characteristics for group A and B were very similar for most parameters with a few exceptions. There was no statistical difference for outcome at 3 years between groups A and B: disease-free survival (DFS) was 45 +/- 1% and 44 +/- 1%, relapse incidence (RI) 41 +/- 1% and 42 +/- 1%, transplant-related mortality (TRM) 23 +/- 1% and 23 +/- 1%, and overall survival (OS) 54 +/- 1% and 55 +/- 1%, respectively, for group A and group B. The real outcome at 3 years for the 5651 patients (group A + group B) transplanted in 1993 was 44 +/- 1%, 41 +/- 1%, 23 +/- 1%, and 54 +/- 1%, for DFS, RI, TRM and OS, respectively. The outcome at 3 years by transplant modality, autologous or allogeneic transplants, and by disease categories showed no difference between groups A and B.     

Evaluation of centre and period effects in allogeneic haematopoietic stem cell transplantation in France

We evaluated the effect of individual and collective factors on the outcome of allogeneic haematopoietic stem cell transplantation (HSCT) at 35 French centres. Individual factors included patient and transplantation characteristics. Collective factors were related to the period and centre in which HSCT was performed. Two centre factors were studied: centre experience (ie number of HSCT performed during the study period) and the type of centre (paediatric or adult). All patients receiving a first allogeneic HSCT in France between 1st January 1993 and 31st December 1997 were included in the study. The follow-up period ended on 31st December 1997. The final sample included 2756 subjects. We analysed overall survival (OS) and transplant-related mortality (TRM). Prognostic factors were identified by univariate and multivariate analysis, using Cox models. We found that centre experience had no significant effect on outcome. However, survival rates, whether determined on the basis of OS or TRM, were significantly higher in paediatric centres than in adult centres. Residual heterogeneity was found between adult centres. Survival rates were significantly higher for HSCT performed after 1st January 1996 than for those performed before this date.     

Invasive fungal infections in allogeneic and autologous stem cell transplant recipients: a single-center study of 166 transplanted patients

OBJECTIVES: Invasive fungal infections (IFIs) remain a major cause of infection-related morbidity and mortality following hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: We retrospectively analyzed the incidence of IFIs in 166 patients undergoing either allogeneic or autologous HSCT at our institution between January 2000 and December 2003. RESULTS: Incidence of invasive aspergillosis (IA) and invasive candidiasis among allogeneic HSCT recipients was 23% (16-32%, 95% confidence interval [CI]) and 3% (1-9%, 95% CI), respectively. Duration of neutropenia and reduced-intensity conditioning were the only risk factors for IA in the multivariate model. Patients with IA had significantly reduced overall survival (8% versus 56%, P=0.01) due to higher transplant-related mortality (63% versus 31%, P=0.03). Following autologous HSCT, incidence of IA and invasive candidiasis was 8% (4-19%, 95% CI) and 2% (0.2-11%, 95% CI), respectively. Duration of neutropenia was the only risk factor for the development of IA following autologous HSCT. Overall survival of autologous HSCT recipients with IA was similar to that of patients without IA. Seventeen percent of autologous HSCT recipients were colonized with Candida species. Compared with non-colonized patients these patients had significantly reduced overall survival (72% versus 23%, P=0.004), due to increased treatment-related mortality (23% versus 9%, P=0.02). CONCLUSION: Diagnosis of IA following allogeneic HSCT and Candida colonization in the setting of autologous HSCT defines patient populations with poor outcome but primarily not as a result of the fungal pathogen. Regarding the incidence of IA, duration of neutropenia is the main risk factor, and dose-reduced conditioning is an additional risk factor for the development of IA following allogeneic HSCT, probably owing to increased recipient age in this patient cohort, requiring further studies in this transplantation setting.     

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.     

Twenty Years’ Experience in Allogeneic Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome—Positive Acute Lymphoblastic Leukemia in the Nagoya Blood and Marrow Transplantation Group

Between October 1981 and December 2000, 46 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) underwent allogeneic hematopoietic stem cell transplantation (HSCT) in the Nagoya Blood and Marrow Transplantation Group. The median age was 28.5 years (range, 4-51 years). All but one patient achieved engraftment. Grade II-to-IV acute graft-versus-host disease (GVHD) developed in 32.5% of patients, and chronic GVHD developed in 40.5%. The incidences of relapse and treatment-related mortality (TRM) at 5 years were 65% and 26%, respectively. The estimated overall survival rate at 5 years was 23%. Univariate analysis showed that improved disease-free survival (DFS) was independently associated with complete remission (CR) at transplantation (39%), compared with non-CR (8%) (P = .023). Non-CR at transplantation was associated with a higher risk of relapse. Donor type, acute GVHD, and time from diagnosis to HSCT all had a significant effect on TRM. In a multivariate analysis, 9 months or more from diagnosis to HSCT was the only variable statistically significant for DFS (relative risk, 3.22; P = .01). This study demonstrates that allogeneic HSCT cures a significant population of patients with Ph+ ALL. Relapse is the major obstacle limiting the success of HSCT. Early transplantation during CR from donors, including unrelated persons or mismatched relatives, may offer improved long-term DFS.