Unrelated donor marrow transplantation for chronic myelogenous leukaemia

Between January 1989 and July 1995 the search for an unrelated donor (UD) was started for 379 consecutive Italian patients with Philadelphia positive (Ph⁺) chronic myelogenous leukaemia (CML). 89 (23%) were transplanted. The overall probability of transplant before and after December 1991 was 16% and 49%, respectively (P = 0.0001), and average interval between search activation and graft was 23 months and 13 months, respectively (P = 0.0001). Disease-free survival (DFS) following 60 consecutive transplants performed before February 1996 was 41.5% at 48 months and was 64% for patients grafted after January 1993. In univariate analysis, five variables had a favourable effect on DFS: year of bone marrow transplantation (BMT) after 1993 (P = 0.0002), HLA-DRB1 donor/recipient (D/R) match (P = 0.0006), total body irradiation (TBI) containing regimen (P = 0.0006), graft-versus-host disease (GvHD) prophylaxis including ‘early’ cyclosporin before the transplant, and a marrow cell dose > 3 × 10⁸/kg of recipient body weight (P = 0.04). Multivariate analysis confirmed that HLA identity (P = 0.006), TBI-containing regimen (P = 0.0001) and ‘early cyclosporin’ (P = 0.04) were associated with higher DFS. Transplant-related mortality (TRM) was 67% in patients grafted before January 1993 and 30% in patients grafted subsequently (P = 0.002). Multivariate analysis confirmed DRB1 identity (P = 0.03) and TBI-containing regimen (P = 0.0005) to be independent factors predictive of low TRM. This suggests that the outcome of patients transplanted from an HLA DRB1 matched donor, after a TBI-containing preparative regimen, is similar to results recently reported in patients transplanted from geno-identical siblings. These results indicate that the search should be initiated at diagnosis for patients < 45 years of age and UD BMT should be considered early in the disease course for those with an available DRB1-matched unrelated donor.     

Unrelated donor bone marrow transplantation for children with relapsed acute lymphoblastic leukaemia in second complete remission

Allogeneic sibling bone marrow transplantation (BMT) is the recommended treatment for relapsed childhood acute lymphoblastic leukaemia (ALL), but appropriate donors are only available in 30% of cases. Unfortunately, BMT from unrelated donors (UD) has been associated with high rates of severe graft-versus-host disease (GvHD) and transplant-related mortality (TRM). In an attempt to improve outcome in UD-BMT we have assessed the impact of T-cell depletion using CAMPATH-1 (anti-CD52) monoclonal antibodies in 50 consecutively referred patients with relapsed ALL in second remission. All were previously treated according to MRC protocols UKALL X and XI, and then given chemotherapy on MRC R1 from relapse until UD-BMT. 19 patients had relapsed on and 31 off therapy.
Patients and donors were fully matched at HLA-A, -B, -DR and -DQ loci in 29 cases and mismatched in 21 (four mismatched for more than one antigen). Pre-transplant conditioning comprised CAMPATH-1G, cyclophosphamide and total body irradiation. Bone marrow was T-cell depleted in vitro using CAMPATH-1 antibodies. Additional GvHD prophylaxis consisted of cyclosporin A (42 cases), cyclosporin plus methotrexate (four) or none (four). 47 patients engrafted. The incidence of acute GvHD was very low: two patients with grade II disease in the matched group, four with grade II–IV in the mismatched group. Only four patients have chronic GvHD. The actuarial event-free survival (EFS) at 2 years is 53%, with no significant difference between the matched and mismatched group. Further leukaemic relapse was the most important cause of failure.
These results are similar to the most favourable published reports for HLA-matched sibling BMT in relapsed ALL.     

Unrelated donor marrow transplantation in children with severe aplastic anaemia using cyclophosphamide, anti-thymocyte globulin and total body irradiation

We report a favourable outcome in 15 patients with severe aplastic anaemia (SAA) who were < 20 years of age and who underwent bone marrow transplantation (BMT) from a human leucocyte antigen (HLA)-matched unrelated donor. All patients were non-responders to intensive immunosuppressive therapy (IST) and were multiply transfused. The conditioning regimen consisted of cyclophosphamide (60 mg/kg/d, on d -4 and -3), anti-thymocyte globulin (2.5 mg/kg/d, on d -5 to -2) and total body irradiation (2.5 Gy x 2/d, on d -2 and -1). Patients received cyclosporine and methotrexate for prophylaxis of graft-versus-host disease (GVHD), except for the last four who received tacrolimus instead of cyclosporine. Donor/recipient pairs were identical for HLA class I and II antigens by serological typing, but four pairs were found to have a mismatch at the HLA-A, -B or -DRB1 locus by high-resolution typing. All patients achieved rapid engraftment and are alive at 2-86 months after transplantation (median follow-up, 51 months). Moderate to severe acute GVHD occurred in 5 out of 15 patients (33%); only one patient developed extensive chronic GVHD. Considering our encouraging results, unrelated donor transplantation for SAA is recommended as a salvage therapy in non-responders to IST.     

Unrelated donor bone marrow transplantation in children and young adults with acute myeloid leukaemia in remission

The role of unrelated donor bone marrow transplantation (UD-BMT) in the management of patients with acute myeloid leukaemia (AML) is uncertain. We describe 18 patients with a median age of 13 years (range 4–31) who received an ex vivo T-cell-depleted UD-BMT for AML (13 in second complete remission (CR2) and five in first complete remission (CR1) with high-risk features). Nine donor recipient pairs were fully matched; eight of these donor–recipient pairs had a single class I HLA mismatch; one patient had both single class I and class II HLA mismatches. Grade II GVHD of the skin occurred in four patients (22%) and limited chronic GVHD in two patients (11%). There have been four deaths: one from relapse and three from infection. With a median follow-up of 27 months, 14 patients survive and the actuarial event-free survival at 2 years is 70 ± 20% (95% confidence interval). We conclude that unrelated donor BMT can result in prolonged disease-free survival in children and young adults with AML.     

Long-term follow-up of patients after related- and unrelated-donor bone marrow transplantation for chronic myelogenous leukemia

 Between January 1983 and December 1997, 88 patients (36 female, 52 male, median age 37 years, range 19–57) with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) at the University Hospital of Vienna. Sixty patients were in chronic phase, 18 in accelerated phase, and ten in blast crisis. Marrow donors were HLA-identical siblings for 64 patients (BM 58, PBSC 6), 2-antigen-mismatched related donors (RD) for two, HLA-identical unrelated donors (URD) for 17, and 1-antigen-mismatched URD for five. The median time from diagnosis to BMT was 22 months (range 2–91), and 63 patients had received prior interferon (IFN)-alpha therapy, 46 (73%) for more than 6 months. Conditioning therapy consisted of cyclophosphamide (CY) and total body irradiation (TBI) in 71 patients and CY and busulfan (BU) in 16. One patient received etoposide and TBI. For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) was given to 12 patients, MTX and cyclosporin A (CSA) to 67, CSA alone to four, and CSA and methylprednisolone to five. Durable engraftment was documented in 80 of 82 patients (98%). As of December 31, 1997, 52 patients (59%) were alive, 38 (58%) after sibling transplantation with a median observation time of 73 months and 14 (64%) after URD transplantation with a median observation time of 12 months. Probability of overall survival is 59%, for patients undergoing transplantation in chronic phase and 44% for patients undergoing transplantation in advanced stage CML. Probability of disease-free survival (DFS) after sibling and URD BMT is 55% and 59%, respectively. Ten patients (12%) experienced relapse of CML. Transplant-related mortality was 32% both after RD and after URD transplantation. Acute GVHD occurred in 53 of 80 evaluable patients (66%), consisting of grade III or IV in 14 patients (18%). Chronic GVHD developed in 40 of 63 eligible patients (63%), including extensive disease in 26 patients (41%). Thus, sibling and URD BMT offer high cure rates with acceptable toxicity to patients with CML. Received: October 27, 1998 / Accepted: May 25, 1999     

Unrelated donor bone marrow transplantation therapy for chronic myelogenous leukemia

Eight patients received allogeneic bone marrow transplantation (BMT) as therapy for chronic myelogenous leukemia (CML) using marrow from unrelated donors. In all cases donors and recipients were HLA DR identical and had low MLC reactivity. In three cases recipients received marrow that was identical at the HLA A,B loci. In five cases HLA identity differed for one HLA A locus antigen. The unrelated donor search interval ranged from 2 to 28 months (median, 3 months). All recipients were prepared with a combination of cyclophosphamide, 60 mg/kg/d administered intravenously (IV) (days -6,-5) and with total body irradiation administered in 165 cGy fractions twice daily for four days (days -4, -3, -2, -1). Engraftment occurred in all cases (range, 18 to 48 days; median, 35 days), and return to a complete Philadelphia chromosome (Ph') negative state was documented in six of eight cases. Moderate or severe acute graft v host disease (GVHD) occurred in seven of eight cases, and extensive chronic GVHD in four of six evaluable recipients. A B cell lymphoproliferative disorder developed in one patient. Four recipients have died within 2 to 4 months of transplant. Four of eight patients survive at 11+ to 24+ months following transplantation (median, 15+ months) with normal peripheral blood counts and without evidence of leukemia. Current Karnofsky activity assessments are 90% or 100% in all survivors. Curative therapy of CML has been available only to the minority of patients eligible for sibling donor BMT. Unrelated donor BMT can be effective in the treatment of CML and may be particularly useful in this disorder since the prolonged stable phase of disease offers an opportunity to locate suitable donors.     

Unrelated donor bone marrow transplantation for children and adolescents with aplastic anaemia or myelodysplasia

Allogeneic transplantation from an HLA-matched family member has been shown to be effective in reconstituting normal haemopoiesis in young people with severe cytopenias, classified as myelodysplastic syndrome (MDS) or severe aplastic anaemia (SAA). Unrelated donor transplant is a therapeutic choice for patients without a suitable family member donor. We report the outcome of seven patients < 20 years old with SAA and 10 with MDS treated with BMT from an HLA A,B DRB1 matched ( n  =8) or A or B locus mismatched ( n  =9) unrelated donor at the University of Minnesota between March 1988 and August 1995. Primary graft failure occurred in two patients and secondary graft failure in one, who was subsequently successfully engrafted with a second donor marrow infusion. Grades II–IV GVHD occurred in 10/16 (63%), and grades III–IV in 6/16 (37%) evaluable patients. Nine of the 17 patients (six with MDS and three with SAA) survive with full donor chimaerism, a median of 1.2 years post-BMT (range 3 months to 7 years). We recommend early referral for consideration of unrelated donor BMT for young patients with MDS, and patients with SAA without response to immunosuppression.     

Unrelated donor bone marrow transplantation to treat severe aplastic anaemia in children and young adults

Alternative donor bone marrow transplantation (BMT) to treat severe aplastic anaemia (SAA) in children and young adults has been complicated by high rates of graft rejection and severe graft-versus-host disease (GVHD). We hypothesized that increased immunosuppression combined with T-cell depletion of the marrow graft would enable successful use of unrelated donor BMT in this disease. Preconditioning consisted of cytosine arabinoside, cyclophosphamide, and total body irradiation (TBI). T-cell depletion was with the anti-CD3 antibody T10B9. GVHD prophylaxis consisted of cyclosporine A. 28 previously transfused patients were transplanted. Nine donor/recipient pairs were HLA matched. As of 1 January 1996, 15/28 (54%) patients are alive, transfusion independent and well with a range of follow-up of 13 months to 8 years (median 2.75 years). Fatalities include all three patients with non-engraftment and all three patients with grade III/IV GVHD. Other fatalities were due to infections or therapy-related toxicity. The incidence ≥ grade II acute GVHD was 28%. These data show that in children with SAA who have failed immunosuppression, unrelated donor BMT offers a reasonable hope of long-term survival.     

Treatment of advanced acute leukaemia with allogeneic bone marrow transplantation from unrelated donors

Summary. Bone marrow transplantation from a histocompatible donor may produce complete remission in patients with induction failure or relapsed acute leukaemia. Through the National Marrow Donor Program, histocompatible bone marrow from unrelated donors has become available for high-risk patients. In this study we analyse the results of matched unrelated bone marrow transplant in 55 patients with highly advanced acute myelogenous and acute lymphoblastic leukaemia. 28 patients with advanced acute lymphoblastic leukaemia and 27 patients with advanced acute myelogenous leukaemia, age 2–51, were treated withy high-dose chemoradiotherapy and transplantation of of 6/6 HLA matched ( n = 46) or one antigen mismatched ( n = 9) unrelated donor bone marrow. After a median follow-up of 36 months, 13 patients remain alive 17–24 months after transplant for a 2-year actuarial disease-free and overall survival of 23 ± 12% (median disease-free survival 3.5 months). The actuarial risk of relapse is 24 ± 16% at 1 year. Moderate to severe graft-versus-host disease occurred in 27/47 evaluable patients (57%). Significant prognostic factors for poor leukaemia-free survival include age >21, abnormal karyotype, and active leukaemia at the time of transplant. Other pretreatment characteristics such as gender or type of leukaemia were not significant prognostic factors. Our results show that matched unrelated bone marrow transplant for patients with advanced acute bone marrow transplant for patients with advanced acute leukaemia may provide long-term leukaemia-free survival, but transplant-related complications produce a sigbificant impact on survival with older age and adverse disease characteristics predicting for poor prognosis     

Infections in adults undergoing unrelated donor bone marrow transplantation

This study retrospectively reviews infections over a 7-year period in 60 consecutive adults (median age 25 years) undergoing their first unrelated donor bone marrow transplant (UD-BMT). T-cell depletion was employed in 93%. More than half the patients had one or more severe, potentially life-threatening, infections. There was a high incidence of invasive fungal infections (Aspergillus 17, Candida four), despite the use of itraconazole or amphotericin prophylaxis. Ten Aspergillus infections occurred beyond 100 d. Two patients (11%) with invasive aspergillosis survived. Clustering of infections was noted, with invasive fungal infections significantly associated with bacteraemias (OR 3.73, P=0.06) and multiple viral infections (OR 4.25, P=0.05). There were 21 severe viral infections in 16 patients, with CMV disease occurring in four patients only; viral pneumonitis was predominantly due to 'community respiratory' viruses. Most early bacteraemias (68%) were due to Gram-positive organisms. The majority of episodes of Gram-negative sepsis were caused by non-fastidious non-fermentative bacteria, such as Pseudomonas spp. and Acinetobacter spp., historically regarded as organisms of low pathogenicity. In patients with successful engraftment and minimal graft-versus-host disease, late infections suggestive of continued immune dysfunction (shingles, recurrent lower respiratory infections, Salmonella enteritis and extensive warts) were common.     

Leukaemic relapse of donor origin after allogeneic bone marrow transplantation from a donor who later developed bronchogenic carcinoma

Donor-derived leukaemia is exceptional after allogeneic bone marrow transplantation (BMT). A woman with chronic myeloid leukaemia received an allogeneic BMT from a human leucocyte antigen-identical brother. The donor, a 50-year-old non-smoker, died of squamous cell bronchogenic carcinoma 1 year later. At 4 years post BMT, the patient became BCR/ABL positive and relapsed with acute myeloid leukaemia, which was shown to be donor-derived cytogenetically and molecularly. Retrospective analysis showed that the donor-leukaemic clone had started to evolve as early as 6 months post BMT. Sequencing of p53 ruled out Li-Fraumeni syndrome. Predisposition to malignancy might be an underlying mechanism of donor-cell leukaemia.     

Acute myeloid leukemia of donor origin after allogeneic bone marrow transplantation for precursor T-cell acute lymphoblastic leukemia: case report and review of the literature

We report a case of donor-derived acute myeloid leukemia (AML) occurring in a 33-year-old man after allogeneic bone marrow transplantation (BMT) for precursor T-cell acute lymphoblastic -leukemia (T-ALL). The cells for BMT were from his human leukocyte antigen (HLA)-matched sister. Fluorescence in-situ hybridization (FISH) analysis showed the AML to be of donor origin (i.e., karyotypically female) with an 11q23 (mixed lineage leukemia (MLL) gene) translocation, while the original T-ALL exhibited a male karyotype with abnormalities of chromosomes 6, 8, and a t(10;14)(q24;q11.2). Subsequent molecular short tandem repeat studies confirmed the AML to be of donor origin. Donor-cell leukemia (DCL) after allogeneic BMT is a rare, yet well-documented, event. Our report presents clinicopathologic information about a case of DCL and a review of the recent literature.     

Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen

We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML.     

Determinants of survival after human leucocyte antigen-matched unrelated donor bone marrow transplantation in adults

Unrelated donor (URD) bone marrow transplantation (BMT) in adults can be associated with high non-relapse mortality (NRM). Therefore, factors determining survival in 136 human leucocyte antigen (HLA)-A, B, DRB1-matched adult BMT recipients were reviewed. Fifty-four per cent of patients had chronic myelogenous leukaemia (CML) and 36% had acute leukaemia or myelodysplasia. Graft-versus-host disease (GvHD) prophylaxis was either cyclosporin A (CSA)/methotrexate (64%) or T-cell depletion and CSA/corticosteroids (34%). The probability of donor engraftment by d 45 was 97% (95% CI: 94-100). Incidence of grades III-IV acute GvHD was 18% (95% CI: 12-24) at 100 d, and chronic GvHD was 42% (95% CI: 32-52) at 2 years. At 2 years, 14% (95% CI: 8-20) had relapsed. Multiple regression analysis showed that adverse risk factors for survival were non-CML diagnosis, age > 35 years, diagnosis to transplant time of > 18 months [chronic-phase CML (CML-CP) only]; and grades III-IV acute GvHD. Patients 35 years with early CML-CP was 55% (95% CI: 33-77), 40% (95% CI: 19-61) in advanced CML and 14% (95% CI:1-27) in non-CML. Future efforts should focus on improving the outcome for older BMT recipients, especially those with diagnoses other than CML.     

Successful bone marrow transplantation from an unrelated donor in a child with AML in second remission

Summary In February 1986 we transplanted a 10-year-old girl with AML in second remission with the bone marrow of an unrelated donor. HLA-types were different for one A- and one B-antigen between patient and donor. Conditioning regimen consisted of 14 Gy total body irradiation with lung shielding, 8×3 g/m² cytosin arabinoside and 90 mg/kg cyclophosphamide. GVHD-prophylaxis was performed with cyclosporin A, methotrexate and prednisolone. Only mild GVHD I of the skin could be observed after rapid engraftment. 100 days after transplantation the patient was in good clinical condition and GVHD-prophylaxis was discontinued without any reactivation of acute or chronic GVHD. Engraftment was documented by sex chromosome and blood group typing. 120 days after transplantation leukemic blasts were detected in the peripheral blood and the child died 130 days after BMT from relapse of the leukemia. Despite the negative outcome, this was the first successful bone marrow transplantation from a unrelated donor in Germany.Supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 120)These authors represent the bone marrow transplantation team in Tübingen     

Outcome of a multicenter treatment program including autologous or allogeneic bone marrow transplantation for de novo acute myeloid leukemia

Abstract: The results of an intensive treatment program for patients 16–60 yr of age with de novo acute myeloid leukemia are presented. The patients were given conventional induction treatment with daunorubicin and cytarabine. Patients not entering complete remission (CR) after 1 course of daunorubicin/cytarabine were given 1 course of amsacrine/etoposide/cytarabine. Those entering complete remission received 3 consolidation courses using mitoxantrone, etoposide, amsacrine and cytarabine. One hundred and eighteen patients were enrolled. Complete remission was attained after 1–2 courses in 90 patients (76%). Another 6 patients reached CR after 3–4 induction courses for a total CR rate of 81%. If feasible, patients were offered either allogeneic or unpurged autologous bone marrow transplantation. Twenty-four patients underwent allogeneic bone marrow transplantation; 15 in first remission, 8 in second remission, 1 in early relapse. Thirty patients below 56 yr of age underwent autologous bone marrow transplantation in first remission. The overall probability of survival at 4 yr was 34%, and for patients below 40 yr of age 50%. Leukemia-free survival was 35% for the whole cohort of patients; 52% for patients below 40 yr of age. Patients undergoing allogeneic or autologous bone marrow transplantation in first remission had an overall survival of 86% and 47%, respectively, while the probability of leukemia-free survival in these groups was 87% vs. 40% at 4 yr. The CR rate and long-term results of this intensive treatment program compare favorably with other recent studies using intensive consolidation with allogeneic or autologous bone marrow transplantation or high dose cytarabine.     

Improved outcome of alternative donor bone marrow transplantation in children with severe aplastic anaemia using a conditioning regimen containing low-dose total body irradiation, cyclophosphamide and Campath

The increasing success of human leucocyte antigen (HLA)-matched sibling donor (MSD) transplants and combination immunosuppressive treatments have dramatically improved the prognosis of severe aplastic anaemia (SAA) in children and young adults. For patients who lack a MSD there is a significant minority who fail immunosuppressive therapy or suffer from a severe constitutional aplastic anaemia in which immunosuppression would be ineffective. Alternative donor bone marrow transplantation (AD-BMT) has only had limited success in this context. We report the successful outcome of AD-BMT in eight consecutive patients aged 7 months to 15 years, six of whom had acquired aplastic anaemia who had previously failed to respond to immunosuppression, and two of whom had a severe (non-Fanconi) constitutional aplastic anaemia. All eight patients had received multiple red cell and platelet transfusions. We used a new combination of agents for pretransplant conditioning aiming to maximize immunosuppression and minimize toxicity, consisting of Campath-1G or -1H, cyclophosphamide and low-dose total body irradiation (LD TBI) or fludarabine. Toxicity was minimal and all eight children are alive, well and free of disease at a median follow-up of 32 months. We suggest that this approach could facilitate the successful treatment of children with SAA in whom immunosuppressive therapy has failed or is not appropriate.     

Elevated levels of soluble ICAM-1 in serum of patients with acute myeloid leukemia undergoing bone marrow transplantation

Serum soluble ICAM-1 concentrations were measured in 10 patients with or without chronic graft-vs.-host disease (GVHD) after allogeneic bone marrow transplantation. The serum soluble ICAM-1 levels in the patients with chronic GVHD were significantly higher than that in the patients without chronic GVHD. The data indicated that serum soluble ICAM-1 is a useful parameter for predicting chronic GVHD. © 1996 Wiley-Liss, Inc.     

Matched and mismatched unrelated donor bone marrow transplantation for juvenile chronic myeloid leukaemia

Juvenile chronic myeloid leukaemia (JCML) is a rare haematological condition of childhood curable only by bone marrow transplantation (BMT). We report our experience using matched and mismatched unrelated donor BMT for JCML in five patients. Although the procedure is hazardous in terms of toxicity and relapse, two patients are alive and disease-free 28 and 49 months post BMT.     

Autologous and allogeneic bone marrow transplantation in acute myeloid leukemia in first complete remission: an update of the Genoa experience with 159 patients

Summary In the attempt to evaluate the role of Autologous and Allogeneic Bone Marrow Transplantation, we have retrospectively analyzed 159 patients with Acute Myeloid Leukemia in first complete remission treated in our Unit, most of whom were referred from other Institutions. High-dose therapy was uniform and consisted of cyclophosphamide 60 mg/kg/d on two consecutive days and TBI in a single dose (10 Gy) for ABMT patients and in fractionated doses (3.3 Gy × 3 days) for BMT patients. Eight years actuarial survival was similar in two groups (52% for BMT and 49% for ABMT). The actuarial risk of relapse for BMT and ABMT was 29% and 43%, respectively. Considering that none of ABMT patients was purged with in vitro technique, this review seems to confirm the importance of in vivo purging with postremission intensification, immediately before the harvesting. Of course, more patients and a longer follow-up are needed to drow final conclusions.