[Is transplantation an alternative to the transfusional impasse in sickle cell disease?] / Dans la drépanocytose, la greffe est-elle une alternative à l'impasse transfusionnelle ?

Sickle cell disease is the most frequent genetic disease in France, concerning 400 newborns each year. The management of these Afro-Caribbean patients requires frequent transfusions from Caucasian donors. Due to important erythroid antigenic differences between Caucasian and African, the prevalence of allo-immunization is high in this population with a risk of transfusional impasse. Allogeneic stem cell transplantation is the only curative treatment for this disease and the replacement of red cells and lymphocytes of the sickle cell patient by those of the donor can also resolve the transfusional impasse. However, a close consultation between physicians from the blood bank and transplantation unit will be required for the choice of conditioning regimen and GvH prophylaxis in order to ensure the transition from a mixed chimerism to the full donor curative graft.

Extensive chronic GVHD is associated with donor blood CD34+ cell count after G-CSF mobilization in non-myeloablative allogeneic PBSC transplantation.

The correlation between the incidence of GVHD and the number of infused CD34(+) cells remains controversial for PBSC transplantation after a reduced-intensity-conditioning (RIC) regimen. We evaluated 99 patients transplanted with an HLA-identical sibling after the same RIC (2-Gy-TBI/fludarabine). Donor and recipient characteristics, donor's blood G-CSF-mobilized CD34(+) cell count, and number of infused CD34(+) and CD3(+) cells were analyzed as risk factors for acute and chronic GVHD There was a trend for an increased incidence of extensive chronic GVHD in the quartile of patients receiving more than 10 × 10(6) CD34(+) cells/kg (P = 0.05). Interestingly, the number of donor's blood CD34(+) cells at day 5 of G-CSF mobilization was closely associated with the incidence of extensive chronic GVHD, that is, 48% (95% CI: 28-68) at 24-months in the quartile of patients whose donors had the highest CD34(+) cell counts versus 24.3% (95% CI: 14-34) in the other patients (P = 0.007). In multivariate analysis, the only factor correlating with extensive chronic GVHD (cGVHD) was the donor's blood CD34(+) cell count after G-CSF (HR 2.49; 95% CI: 1.16-5.35, P = 0.019). This study shows that the incidence of cGVHD is more strongly associated with the donor's ability to mobilize CD34(+) cells than with the number of infused CD34(+) cells.

Double reduced-intensity allogeneic hematopoietic stem cell transplantation: a retrospective study from the SFGM-TC.

The purpose of this paper is to describe the outcome of patients who underwent double allogeneic hematopoietic stem cell transplantation (AHSCT) with reduced-intensity conditioning regimens (RIC). Forty-five patients who received double RIC-AHSCT between 1997 and 2006 were retrospectively studied. The predominant diagnosis was acute myeloid leukemia (AML) (n = 17). Other diagnoses were aplasic anemia (AA) (n = 5), myelodysplasic disorder (n = 5), acute lymphoblastic leukemia (ALL) (n = 4), chronic myelomonocytic leukemia (CML) (n = 3), myeloma (n = 3), non-Hodgkin lymphoma (NHL) (n = 3), chronic lymphocytic leukemia (CLL) (n = 2), Hodgkin's disease (HD) (n = 2), and chronic myelomonocytic leukemia (n = 1). Main indications for RIC-AHSCT 2 were relapse (n = 25, 56%) and early (n = 8, 18%) or late (n = 12, 26%) graft failure. Median delays to reach a neutrophil count of 0.5 × 10(9)/L and platelet counts of 50 × 10(9)/L were significantly smaller after the second AHSCT. Among 25 patients who relapsed after RIC-AHSCT 1, 14 patients (56%) presented a response improvement after RIC-AHSCT 2. In this group, 9 patients sustained a complete response and 5 patients a partial response. Moreover, among the 20 patients who had early or late graft failure following RIC-AHSCT 1, 9 (45%) finally reached an engraftment. Disease-free survival (DFS) was significantly improved after RIC-AHSCT 2. Thirteen patients (28%) died of transplant-related mortality (TRM) at a median delay of 69 days (range: 0-451) after RIC-AHSCT 2. Double RIC-AHSCT is a feasible procedure that allows a response or engraftment not observed after RIC-AHSCT 1. The main indication is relapse. However, TRM remains high.

Evidence for anti-tumour effect of allogeneic haematopoietic SCT in cases without sustained donor engraftment.

Remissions of haematological malignancies have been reported after allo-SCT, despite donor cell rejection, suggesting that sustained allogeneic engraftment is not mandatory to obtain a lasting anti-tumour effect. To evaluate the potential benefit from transient post-allo-SCT alloreactivity, we took advantage of the Société Française de Greffe de Moëlle et Thérapie Cellulaire (SFGM-TC) registry to colligate 14 patients with an efficient and long-lasting allogeneic (GVL) effect after allo-SCT for haematological malignancies, despite transient or absent engraftment. None received a second allogeneic graft after autologous recovery. The median duration of remission after autologous reconstitution was 118 (12-252) months. Although we cannot exclude the possibility that some patients were cured before allo-SCT, this retrospective analysis does strongly suggest that an efficient GVL effect can be observed without sustained donor engraftment, and that the transient presence of donor T cells might be sufficient to induce a powerful GVL effect.

Correlation between galactomannan antigen levels in serum and neutrophil counts in haematological patients with invasive aspergillosis.

The detection of circulating galactomannan (GM) in serum samples is an important step in the diagnosis of invasive aspergillosis (IA). The assay has been mainly explored in neutropenic patients, and is now used to monitor patients at high risk for IA. However, the performance of the assay varies greatly among studies. The objective of this study was to explore the impact of the neutrophil count on the GM serum index at the time of IA diagnosis. Ninety-nine episodes of proven or probable, microbiologically documented IA in 91 patients with haematological malignancies were studied retrospectively. Three groups were identified: groups 1-3, with <100 polymorphonuclear neutrophils (PMN)/mm(3) (n = 18), between 100 and 500 PMN/mm(3) (n = 21), or >500 PMN/mm(3) (n = 60), respectively. The mean GM index was significantly higher in group 1 than in the other groups (p <0.05). This finding did not change after stratifying the analysis with regard to the use of antibiotics likely to give false-positive GM results or with regard to treatment effective against fungi before the diagnosis of IA. This finding could be considered in the routine use of the GM antigenaemia test in non-neutropenic patients; a negative result or a low GM index should not eliminate the diagnosis of IA. This limitation calls for other microbiological tests, including analysis of bronchoalveolar lavage fluid, to establish a definitive diagnosis of IA.

HLA-E upregulation on IFN-gamma-activated AML blasts impairs CD94/NKG2A-dependent NK cytolysis after haplo-mismatched hematopoietic SCT.

Natural killer (NK) cells generated after haploidentical hematopoietic SCT in patients with AML are characterized by specific phenotypic features and impaired functioning that may affect transplantation outcome. We show that IFN-gamma produced by immature CD56(bright) NK cells upregulates cell surface expression of HLA-E on AML blasts and that this upregulation protects leukemic cells from NK-mediated cell lysis through the mediation of CD94/NKG2A, an inhibitory receptor overexpressed on NK cells after haploidentical SCT. Two years after transplantation, however, maturing NK cells were functionally active, as evidenced by high cytotoxicity and poor IFN-gamma production. This implies that maturation of NK cells is the key to improved immune responses and transplantation outcome.

Involvement of mature donor T cells in the NK cell reconstitution after haploidentical hematopoietic stem-cell transplantation.

We previously demonstrated that natural killer (NK) cells generated after haploidentical stem-cell transplantation (SCT) are blocked at an immature state characterized by phenotypic features and impaired functioning and that this may affect transplantation outcome. We hypothesize that the absence of mature donor T cells in the graft may affect NK cell differentiation. NK cells from 21 transplant recipients who underwent either partial (pTCD; n=11) or extensive (eTCD; n=10) T-cell depletion were compared with NK cells from their healthy donors. We report that despite the strong graft-versus-host disease (GvHD) reaction, pTCD patients, with T cells present during SCT, had a better clinical outcome than patients with eTCD transplants. In addition, the frequency of CD3- CD56(bright) and NKG2A+ NK cells was much lower in pTCD than in eTCD patients after transplantation, and the level of cytotoxicity against primary haplo-mismatched blasts was significantly more pronounced after pTCD than eTCD transplants. These finding strongly suggest that mature donor T cells in the graft may play a key role in NK cell differentiation in vivo, after haploidentical SCT.

[Early pneumonia after allogenic stem cell transplantation]. / Complications pulmonaires précoces des allogreffes de cellules souches hématopoïétiques.

INTRODUCTION: Pneumonia is one of the main causes of mortality following allogenic stem cell transplantation, especially in the first months after the transplant has been performed. STATE OF THE ART: Pneumonia is the most common infection occurring after transplant and the infection with the highest mortality. Following the classical, myeloablative approach to transplant, two thirds of the pneumonias that occur are of infectious origin. Their causes roughly follow the timing of the immune reconstitution, and may depend on the type of transplant, the match between donor and recipient, and, overall, the occurrence of graft-versus-host disease. Most bacterial pneumonias occur during the initial neutropenic phase. The 2nd and 3rd month post transplant are mainly complicated by viral pneumonia, especially respiratory virus and adenovirus pneumonia in deeply immunosuppressed patients. Preemptive and prophylactic strategies have considerably reduced the incidence of cytomegalovirus pneumonia. Pneumonia due to encapsulated bacteria, such as Haemophilus influenzae and Streptococcus pneumoniae, usually considered to be late infections, may actually be observed from the second month post-transplant. PERSPECTIVES: The increasing use of reduced-intensity conditioning regimens has modified the time course of the main adverse events following transplantation, including the timing of the infectious pneumonias. The pneumonias that are specifically related to allogenic transplant are idiopathic interstitial pneumonia, bronchiolitis obliterans, and bronchiolitis obliterans organizing pneumonia, which are all considered to be pulmonary manifestations of graft-versus-host disease, and treated as such. Prophylaxis for many of these infectious pneumonias (i.e., P jiroveci, S pneumoniae, toxoplasmosis) are well standardized. CONCLUSIONS: Much remains to be done to decrease the incidence of pneumonia in these patients and to understand their mechanisms.

[ABO incompatibility and non myeloablative allogeneic stem cell transplantation]. / Incompatibilité ABO et greffe allogénique de cellules souches hématopoïétiques à l'ère des conditionnements non myéloablatifs.

ABO incompatibility is not a barrier for allogeneic hematopoietic stem cell transplantation but is associated with specific complications. Major ABO incompatibility is associated with delayed erythroid engraftment, increased transfusion requirement and cases of pure red cell aplasia. Minor ABO incompatibility may be responsible for acute haemolytic reactions in the first months following transplantation. The widely used non myeloablative conditioning regimens might modify the management of ABO incompatibility. They could favour pure red cell aplasia development in the setting of major ABO mismatch since they are associated with a prolonged persistence of host anti-donor isohemagglutinins after allogeneic hematopoietic stem cell transplantation. In the setting of minor ABO incompatibility, the use of peripheral blood stem cells and the nature of graft-versus-host disease prophylaxis regimen may have an impact on the incidence of haemolytic reactions. In that review, the clinical and therapeutic aspects of ABO incompatibility are studied, especially regarding the impact of the conditioning regimen intensity.

Impact of nonmyeloablative conditioning regimens on the occurrence of pure red cell aplasia after ABO-incompatible allogeneic haematopoietic stem cell transplantation.

BACKGROUND AND OBJECTIVES: In the setting of major ABO-incompatible allogeneic haematopoietic stem cell transplantation (HSCT), pure red cell aplasia (PRCA) is linked to the persistence of host residual plasma cells secreting antidonor isohaemagglutinins (HA) after transplantation. There are conflicting results regarding the impact of the intensity of conditioning regimen on the occurrence of PRCA after major ABO-mismatched HSCT. MATERIAL AND METHODS: To address this question, we compared two cases occurring after nonmyeloablative (NMA) and myeloablative (MA) HSCT and reviewed previous cases reported in the NMA setting. RESULTS AND CONCLUSIONS: We observed a delayed disappearance of antidonor HAs in the NMA setting, associated to a more prolonged period of red blood cells transfusion dependence than in the MA setting. In our case as in several others, the disappearance of antidonor HAs and resolution of PRCA were observed after reinforcement of the graft-versus-host effect (i.e. immunosuppression removal or donor leukocytes infusion).

Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study.

Adult patients with acute lymphoblastic leukemia (ALL) and t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4 have a poor outcome. We have evaluated the impact of an intensified post-remission therapy using a high-dose chemotherapy course followed by allogeneic or autologous SCT on the outcome of 58 patients with t(1;19)/E2A-PBX1 (E2A group, n=24) or t(4;11)/MLL-AF4 (MLL group, n=34) treated in the LALA-94 multicenter prospective study. Patients in the MLL group had higher WBC counts and more frequent DIC. CR rates achieved by MLL and E2A groups were similar to other B-cell ALL (87, 82 and 86% respectively). While in CR, patients with a donor were assigned to alloSCT (n=22), the remaining patients with were randomized between autoSCT (n=15) or chemotherapy (n=8). Five-year overall survival was 31 and 45% for E2A and MLL groups, respectively. In both groups, DFS was higher in the alloSCT arm as compared to autoSCT and chemotherapy arms. The results of this study show that chemotherapy intensification did not overcome the poor prognosis of adults with t(1;19)/E2A-PBX1. Allogeneic SCT should thus be offered in first CR to patients with t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4. New therapeutic approaches are needed for patients without donor.

Autologous stem cell transplantation in adults with acute lymphoblastic leukemia in first complete remission: analysis of the LALA-85, -87 and -94 trials.

To evaluate the results of autologous stem cell transplantation (ASCT) in a large population of adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR), we performed an individual data-based overview of the last three trials from the LALA group. Overall, 349 patients with ALL prospectively randomized in the consecutive LALA-85, -87, and -94 trials to receive either ASCT or chemotherapy as post-CR treatment were analyzed. Eligibility criteria were 15-50-year-old patients without sibling donors in both LALA-85/87 trials and 15-55-year-old patients with high-risk ALL and no sibling donors in the LALA-94 trial. Intent-to-treat analysis, which compared 175 patients from the ASCT arm to 174 patients from the chemotherapy arm, showed that ASCT was associated with a lower cumulative incidence of relapse (66 vs 78% at 10 years; P=0.05), without significant gain in disease-free or overall survival. Despite a possible lack of statistical power, a nested case-control analysis performed in 85 patient pairs adjusted for time to transplant and prognostic covariates confirmed these intent-to-treat results in patients actually transplanted. Of interest, the reduced relapse risk after ASCT translated in better disease-free survival in the 300 rapid responders who reached CR after the first induction course.

New findings and key questions in hematopoietic stem cell transplantation.

Invasive aspergillosis remains the primary cause of death from infection following allogeneic stem cell transplantation. Most cases occur during the second or third month after transplantation, during graft-versus-host disease or immunosuppression. Strategies for management of these cases include the development of more effective antifungals for prophylaxis, the use of biological markers to improve the early diagnosis of aspergillosis, new approaches to transplantation to reduce the risk of infection, and the emerging area of targeted cellular therapy.

Do minitransplants have minicosts? A cost comparison between myeloablative and nonmyeloablative allogeneic stem cell transplant in patients with acute myeloid leukemia.

Allogeneic hematopoietic stem cell transplantation (SCT) is a widely used, cost-intensive procedure. Although pretransplant nonmyeloablative (NMA) or reduced-intensity conditioning regimens appear very promising, prospective studies comparing this approach with the conventional myeloablative (MA) approach in specific hematologic diseases are necessary, especially in patients in whom the conventional approach is not contraindicated. Cost may be an important factor in the decision-making process. We compared the costs of MA and NMA transplants in patients with acute myeloid leukemia (AML). We estimated 1-year resource utilization in 12 consecutive MA patients (median age: 39 years) and in 11 consecutive NMA patients (median age: 58 years) who underwent HLA-identical sibling SCT for AML. Resources care expenses were valued using the average daily rate for personnel costs, supplies, and room costs. Other data were directly collected from the patients' charts. Despite a trend for lower costs in NMA patients during the first 6 months, costs during the 6-12-month period were significantly higher after NMA due to late complications and readmissions (P=0.03). Finally, mean 1-year costs were not different in MA and NMA patients (P=0.75). Prospective studies comparing conventional and NMA approaches in homogeneous populations should include economic items.

Calcineurin activity as a functional index of immunosuppression after allogeneic stem-cell transplantation.

BACKGROUND: The authors have previously shown that mononuclear cells derived from patients with resistant chronic graft-versus-host-disease (GVHD) express high calcineurin (CN) activity, suggesting that in vitro assessment of CN activity may be a useful index to estimate the degree of immunosuppression afforded by cyclosporine A (CsA). The goal of this study was to assess CN activity during the first 2 months after allogeneic stem-cell transplantation (SCT) and to correlate its evolution with the occurrence of acute GVHD. METHODS: Thirty-one allogeneic SCT recipients were enrolled during a 21-month period. All received GVHD prophylaxis with CsA (2 mg/kg/day) and methotrexate (on days 1, 3, and 6). CN activity was measured before transplant, and then once weekly, for at least 2 months. RESULTS: Eighteen patients developed acute grade II or higher GVHD at a median time of 22.5 days and were treated with steroids. CN activity was significantly increased in these 18 patients when compared with 13 patients who did not develop GVHD. Analysis involving the receiver operating characteristic curve demonstrated that acute grade II or higher GVHD can be predicted with a sensitivity of 89% and a specificity of 54% with the use of a cutoff value of 28 pmol RII/mg proteins/min of CN activity. CONCLUSIONS: CN activity appears to be a promising therapeutic test to predict acute GVHD after allogeneic SCT. This functional assessment of the in vivo efficacy of CsA opens new insights for CsA dose adjustment-in particular, the administration of its most efficient dose instead of its maximal tolerated dose, as is currently performed.

Secondary antifungal prophylaxis with voriconazole to adhere to scheduled treatment in leukemic patients and stem cell transplant recipients.

Although the efficacy and safety of voriconazole to treat invasive fungal infections have been demonstrated in prospective trials, its use for secondary prophylaxis to prevent reactivation of these infections remains unknown. Delaying the scheduled treatment of leukemia until complete resolution of fungal infection may have major implications for prognosis. We report 11 leukemic patients with previous aspergillus (n=10) and candida (n=1) infection who received voriconazole 400 mg/day intravenously or orally for between 44 and 245 days. Nine patients were scheduled for allogeneic stem cell transplant, and two for consolidation therapy for acute leukemia. None of the patients had a relapse of fungal infection, and scheduled treatment was delayed only once. Voriconazole was well tolerated, except in one patient who had abnormal liver tests secondary to hepatic graft-versus-host disease, and one who had visual disturbances. This small but homogeneous series indicates that voriconazole may be useful to prevent fungal relapse during at-risk periods in leukemic patients. Prospective trials are warranted to confirm these encouraging results.

A potential graft-versus-leukemia effect after allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: results from the French Bone Marrow Transplantation Society.

SUMMARY: Philadelphia chromosome (Ph) acute lymphoblastic leukemia-positive (ALL) is a subgroup of ALL with a poor prognosis. We sought to evaluate the results of allogeneic hematopoietic stem cell transplantation (HSCT) in this situation. From 1992 to 2000, 121 patients with Ph- positive ALL enrolled in one of the three main French prospective ALL chemotherapy trials and receiving allogeneic HSCT were reported to the registry of the French Society of Bone Marrow Transplantation (SFGM-TC). The median age was 35 years (range, 1-53). In all, 76 patients received HSCT in first complete remission and 45 in a more advanced disease stage. Minimal residual disease was evaluated just before the graft: 35 patients of the 52 patients in first remission had persistent BCR-ABL transcript detectable while 17 had no detectable minimal residual disease. Bone marrow and/or peripheral blood samples from 94 patients were submitted for reverse transcriptase polymerase chain reaction analysis at variable points after transplantation. Estimated 2-year survival and relapse rate for patients in CR1 were 50 and 37%, respectively, significantly better than for patients with more advanced disease (P=0.0001 and 0.01, respectively). There was no difference in survival or in relapse rates in terms of the donor used. Relapse was the most common cause of treatment failure. Hematological status at the time of transplant and the occurrence of acute graft-versus-host disease (GvHD) were the only two prognostic factors identified for relapse (P=0.02 and 0.02, respectively). Detection of BCR-ABL transcripts after transplantation had a predictive value on relapse occurrence. Finally, donor lymphocyte infusions were successfully used to treat some relapses. The graft-versus-leukemia effect of HSCT in Ph-positive ALL appears to be supported by (1) the lack of prognostic significance of pretransplant BCR-ABL transcript detection, (2) the efficacy of donor lymphocyte infusions in cases of relapse, and (3) the role of GvHD as protecting against relapse.

Higher doses of CD34+ peripheral blood stem cells are associated with increased mortality from chronic graft-versus-host disease after allogeneic HLA-identical sibling transplantation.

Allogeneic peripheral blood stem cell transplantation (PBSCT) has emerged as an alternative to bone marrow transplantation. PBSCT can be associated with a higher incidence of chronic graft-versus-host disease (cGVHD). In this study, we investigated whether there was a correlation between the composition of PBSC grafts (CD34+ and CD3+ cells) and hematological recovery, GVHD, relapse, and relapse-free survival (RFS) after myeloablative HLA-identical sibling PBSCT. The evolution of 100 acute or chronic leukemia patients was analyzed. Neither hematological recovery, acute or cGVHD, nor relapse, was significantly associated with CD3+ cell dose. Increasing CD34+ stem cells was associated with faster neutrophil (P=0.03) and platelet (P=0.007) recovery. Moreover, 47 of the 78 patients evaluable for cGVHD (60%; 95% CI, 49-71%) developed extensive cGVHD. The probability of extensive cGVHD at 4 years was 34% (95% CI, 21-47%) in patients receiving a 'low' CD34+ cell dose (<8.3 x 10(6)/kg), as compared to 62% (95% CI, 48-76%) in patients receiving a 'high' CD34+ cell dose (>8.3 x 10(6)/kg) (P=0.01). At a median follow-up of 59 months, this has not translated into a difference in relapse. In patients evaluable for cGVHD, RFS was significantly higher in patients receiving a 'low' CD34+ cell dose as compared to those receiving a 'high' CD34+ cell dose (P=0.04). This difference was mainly because of a significantly higher cGVHD-associated mortality (P=0.01). Efforts to accelerate engraftment by increasing CD34+ cell dose must be counterbalanced with the risk of detrimental cGVHD.

Healthy sibling donor anxiety and pain during bone marrow or peripheral blood stem cell harvesting for allogeneic transplantation: results of a randomised study.

This study reports the first comparison of healthy donor subjective well-being during two alternative procedures of hematopoietic stem cells harvesting for allogeneic transplantation. Among the 105 donors included between September 1996 and October 1998 in the SFGM French randomised trial aiming to compare allogeneic bone marrow (BM) transplantation and blood cell (BC) transplantation, 64 donors (33 in BC and 31 in BM groups) were relevant for the analysis. They had received a set of self-administered questionnaires to complete during the collection process, aiming to measure anxiety (assessed using the Spielberger's State-Trait Anxiety Inventory) and pain induced by the procedure (evaluated using a visual analogical scale). Results showed that no harvest procedure is free from pain even if none was more painful than the other. Levels of anxiety before the collection procedure were high in both groups and significantly so for BC donors. Although BC collection induces at least similar levels of pain and anxiety as does BM collection, they were of a different kind, and the short-term impact of G-CSF stimulation on the well-being of BC donors has to be taken into account in improving quality of care in the allogeneic setting.

Prior treatment with alpha interferon does not adversely affect the outcome of allogeneic transplantation for chronic myeloid leukaemia.

The timing of transplantation in chronic myeloid leukaemia is still debated and previous treatment with interferon (IFN) alpha has been reported to be deleterious. We have analysed the outcome of 438 allogeneic transplants performed between 1984 and 1995 and reported to the Société Française de Greffe de Moelle (SFGM) registry. One hundred and two patients (group I) received IFN for more than 6 weeks (median = 9 months) before transplant. Their outcome was compared with 336 other patients (group II) not pretreated with IFN. There were no significant differences between the groups for engraftment and chronic graft-versus-host disease (GVHD) incidence. However, other significant differences included the incidence of acute GVHD > or = 2 at 3 months which was higher in group I (65 +/- 10%) than in group II (38 +/- 5%; P = 0.01). Moreover, disease-free survival (DFS) and overall survival (OS) at 5 years were significantly shorter for group I than for group II (33 +/- 10% vs. 41 +/- 6%; P = 0.005)(95% CI) and (41 +/- 10% vs. 55 +/- 6%; P = 0.002)(95% CI) respectively. After adjustment for patient and transplant covariables in a multivariate analysis, prior IFN was not found to adversely affect transplant outcome.