Allogeneic bone marrow transplantation with T-cell-depleted marrow grafts for patients with poor-risk relapsed low-grade non-Hodgkin's lymphoma

We present the clinical results of allogeneic bone marrow transplantation (BMT) with T-cell-depleted grafts from HLA-matched sibling donors in patients with poor-risk relapsed low-grade non-Hodgkin's lymphoma (NHL). Poor risk was defined as relapse within 12 months after or progression during prior treatment. The conditioning regimen consisted of cyclophosphamide and total-body irradiation with or without additional idarubicin. Donor marrow was depleted of T lymphocytes using counterflow centrifugation. Post-BMT prophylaxis of graft-versus-host disease (GvHD) consisted of cyclosporine A. 15 patients with a median age of 47 years (range 30–57) were transplanted. All patients engrafted. After a median follow-up of 36 months (range 9–78), 10 patients were alive and in complete remission (CR). Two of them had relapsed after BMT but re-entered CR following infusions of leucocytes from the original bone marrow donor. Five patients died; causes of death were cardiomyopathy ( n  = 1), chronic GvHD ( n  = 1) and infection during chronic GvHD ( n  = 3). We conclude that allogeneic T-cell-depleted bone marrow transplantation is an efficacious treatment for patients with poor-risk relapsed low-grade NHL. Infusions of donor leucocytes reinduced CR in the two patients with relapse after BMT.     

Busulfan and cyclophosphamide as a preparative regimen for allogeneic blood and marrow transplantation in patients with non-Hodgkin's lymphoma

This study reports on overall and recurrence-free survival (OS and RFS) of 37 consecutive patients with low- and intermediate-grade NHL receiving a related donor allogeneic BMT using a nonradiation-containing preparative regimen. In addition, transplant-related toxicity and factors influencing outcome are discussed. The preparative regimen consisted of busulfan and cyclophosphamide. Median patient age was 44 years (range 20-55). In all, 18 were female. Median follow-up of surviving patients from BMT was 4.2 years. A total of 25 patients had low-grade, and 12 intermediate grade NHL. Most patients (89%) were treated with at least two different chemotherapy regimens prior to BMT. In all, 22 patients (59%) were transplanted in partial remission, 15 (41%) in complete remission. OS at 12 months was 89% (95% confidence interval (CI) of 79-99%) and 79% (64-93%) at 60 months. RFS at 12 months was 86% (75-97%) and at 5 years 70% (54-86%). Four patients (11%) relapsed. Seven patients (19%) died, six because of treatment-related toxicity and one with relapse. Univariate analysis showed improved OS for younger patients and patients of female gender, suggesting that allogeneic BMT using busulfan-cyclophosphamide as a preparative regimen can achieve disease control and possibly cure patients with NHL particularly younger ones.     

Predictors of response to reinduction chemotherapy for patients with acute myeloid leukemia who do not achieve complete remission with frontline induction chemotherapy

Eighty-one patients with acute myeloid leukemia who had persistent leukemia following standard induction therapy with cytarabine plus daunorubicin (7+3 regimen) underwent reinduction therapy with a combination of mitoxantrone, etoposide, and high-dose cytarabine (HiDAC). Patients achieving complete remission (CR) then received consolidation therapy with HiDAC plus mitoxantrone. Patients with matched sibling donors were referred for allogeneic bone marrow transplantation (BMT) in CR-1. The overall response rate to reinduction was 53%. The major adverse predictors of CR on multivariate analysis were poor risk cytogenetics, a higher % bone marrow blasts prior to reinduction therapy and increased age. The median relapse-free survival (RFS) was 9 months and the estimated 2-year RFS was 30%. No significant predictors of RFS or overall survival (OS) were found among the patients achieving CR. Patients undergoing allogeneic BMT in CR-1 after double induction had a 50% 2-year OS. Patients relapsing after achieving CR with double induction had a poor outcome with a 4% 1-year OS. The results indicate that patients with poor risk cytogenetics or marrow blast percentage >or= 60% following 7+3 induction have a low probability of achieving CR with reinduction and should be considered for novel approaches to improve CR rates. Patients achieving CR are at high risk of relapse and should be considered for allogeneic BMT or novel strategies to attempt to reduce relapse rates.     

Long-term results of allogeneic bone marrow transplantation for 108 adult patients with acute lymphoblastic leukemia: favorable outcome with BMT at first remission and HLA-matched unrelated donor

We analyzed the outcome of 108 adult acute lymphoblastic leukemia patients undergoing allogeneic bone marrow transplantation (BMT). Philadelphia (Ph) chromosome occurred in 35.2% patients at diagnosis. Two-thirds of patients received allogeneic BMT in first complete remission (CR1) BMT. Salvage BMT was performed in 21 and 16 patients at second complete remission (CR2) and beyond CR2. Donors were human leukocyte antigen-identical siblings in 87 patients, and match-unrelated donors in 21 patients. Conditioning contained total body irradiation (TBI) in 92.6% patients. Overall survival (OS) for BMT at CR1 and BMT beyond CR1 were 46.2 and 20.3% at 15 years. Multivariate analyses (including age, sex, disease status, donor type, acute graft-versus-host disease (aGVHD), stem cell source, cytogenetics, grade 1/2 aGVHD and TBI-containing conditioning regimen) identified age<35, BMT at CR1 and grade 1/2 aGVHD as favorable factors for OS. Disease-free survival (DFS) for BMT at CR1 and beyond CR1 were 45.8 and 15.9% at 15 years, respectively, with BMT at CR1, age<35 and grade 1/2 aGVHD being favorable factors for DFS. Importantly, conventional adverse risk factors such as the Ph chromosome, B-cell phenotype and high leukocyte count were not associated with inferior survivals. In summary, the adverse impact of Ph chromosome, B-cell phenotype and high leukocyte count was overcome by allogeneic BMT. Matched unrelated donor transplantation appears promising.     

An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation

The role of allogeneic bone marrow transplantation in lymphoma remains uncertain. We have analyzed 1185 allogeneic transplants for lymphoma reported to the EBMT registry between 1982 and 1998 and compared the results with those of 14687 autologous procedures performed over the same period. Patients receiving allogeneic transplants were subdivided according to histology: low-grade non-Hodgkin's lymphoma (NHL) 231 patients; intermediate-grade NHL 147 patients; high-grade NHL 255 patients; lymphoblastic NHL 314 patients; Burkitt's lymphoma 71 patients; and Hodgkin's disease 167 patients. These patients received allogeneic transplants as their first transplant procedure. Actuarial overall survival (OS) at 4 years from transplantation was: low-grade NHL 51.1%; intermediate-grade NHL 38.3%; high-grade NHL 41.2%; lymphoblastic lymphoma 42.0% years; Burkitt's lymphoma 37.1%; and Hodgkin's disease 24.7% years. These outcomes are relatively poor because of the high procedure-related mortality associated with these procedures, particularly in patients with Hodgkin's disease (51.7% actuarial procedure-related mortality at 4 years). Multivariate analysis showed that for all lymphomas apart from Hodgkin's disease, status at transplantation significantly affected outcome. A matched analysis was performed: for all categories of lymphoma, OS was better for autologous than for allogeneic transplantation. Relapse rate was better in the allogeneic group for low-, intermediate- and high-grade, and lymphoblastic NHL. It was equivalent for Burkitt's lymphoma and worse in the allogeneic group for Hodgkin's disease. Allogeneic transplantation appears to be superior to autologous procedures in terms of producing a lower relapse rate. The toxicity of allogeneic procedures must however be reduced before this translates into an improvement in OS.     

Allogeneic haematopoietic stem-cell transplantation for relapsed and refractory aggressive histology non-Hodgkin lymphoma

Forty-four patients with relapsed or refractory aggressive histology non-Hodgkin lymphoma (NHL) (diffuse large B cell, n = 23; peripheral T cell, n = 5; transformed B cell, n = 16) proceeded to allogeneic stem cell transplant (allo-SCT) between 1987 and 2003. Median age at transplant was 40 years (range 19-56 years). At the time of transplant, 35 were chemosensitive and nine were chemorefractory. Thirty-three patients had matched sibling donors and 11 had unrelated donors. Forty-two patients (95%) received radiation-based conditioning regimens. Event-free survival (EFS) and overall survival (OS) at 5 years was 43% [95% confidence interval (CI): 27-58%] and 48% (95% CI: 32-63%) respectively. Treatment-related mortality was 25% at 1 year. Grade III-IV acute graft-versus-host disease (GVHD) was the only significant variable affecting OS and EFS, and had a negative impact. Chronic GVHD did not influence survival. Lymphoma relapse <12 months after initial therapy predicted for increased risk of relapse post-transplant (P = 0.02). Patients with chemorefractory lymphoma were not at increased risk of relapse (P = 0.20) with four of nine patients remaining alive without disease 12-103 months post-transplant. In conclusion, allo-SCT for relapsed or refractory aggressive histology NHL results in long-term EFS and OS of 40-50%. Patients with chemorefractory disease can have a durable remission post-transplant.     

Total body irradiation–high-dose cytosine arabinoside and melphalan followed by allogeneic bone marrow transplantation from HLA-identical siblings in the treatment of children with acute lymphoblastic leukaemia after relapse while receiving chemotherapy: a Société Française de Greffe de Moelle study

We investigated the use of a new conditioning regimen followed by allogeneic bone marrow transplantation (BMT) for treating children with acute lymphoblastic leukaemia (ALL) after relapse within 6 months of the completion of therapy. One hundred and sixteen children with acute lymphoblastic leukaemia in second or subsequent complete remission (CR) underwent allogeneic bone marrow transplantation from HLA-identical siblings after a preparative regimen comprising total body irradiation (TBI), high-dose cytosine arabinoside and melphalan (TAM regimen). The Kaplan-Meier product-limit estimate (mean ± SE) of disease-free survival (DFS) at 7 years was 59.5 ± 9% (95% confidence interval). The estimated chance of relapse was 22.5 ± 15% with a median follow-up of 88.5 months (range 51–132). 26 patients (22.4%) died with no evidence of recurrent leukaemia, mainly from interstitial pneumonitis, veno-occlusive disease or acute graft-versus-host disease (GVHD). Three factors significantly affected DFS: acute GVHD, site of relapse and, for children in second remission after a marrow relapse, the disease status at the time of transplantation. The DFS were 59.02 ± 12.6%, 37.5 ± 19.8% and 77.4 ± 15% among patients in CR2 after a marrow relapse, in CR3 or in untreated partial marrow relapse, and in CR2 after an isolated CNS relapse, respectively. The lowest DFS was seen in children with acute GVHD grades 3–4. Two significant factors were associated with relapse: the marrow status at the time of transplantation and chronic GVHD. The relapse rate was lower among children in CR2 or with chronic GVHD. We conclude that transplantation after the TAM regimen is an effective therapy for this population with acceptable toxicity, particularly for children in second remission after a very early marrow relapse, or those with early isolated CNS involvement.     

Allogeneic or autologous bone marrow transplantation (BMT) for non-Hodgkin's lymphoma (NHL): results of a provincial strategy. Ontario BMT Network, Canada

In 1986, the bone marrow transplant centers in Ontario agreed to a strategy for the treatment of patients with NHL. Suitable patients would undergo autotransplant but be referred for allotransplant if they had persistent marrow involvement or an inadequate marrow/stem cell harvest. Data of all patients were recorded in a database. We reviewed this database to compare these transplant modalities with respect to overall survival, rate of relapse and treatment-related mortality. Between January 1986 and August 1997, 429 patients underwent BMT for NHL - 385 autotransplants and 44 allotransplants. Sixty-eight percent of patients received their transplant for aggressive NHL, while the others had indolent lymphoma. Three-year actuarial survival did not differ between allogeneic and autologous BMT: 71% vs 62%, respectively (P = 0.5330 by log-rank testing). Three-year actuarial rate of relapse was lower after allotransplant than autotransplant: 6% vs 41%, respectively (P = 0.0006 by log-rank testing). Treatment-related mortality was higher after allotransplant than autotransplant: 23% vs 6%, respectively (P = 0.001 by chi2 analysis). For further comparison, autotransplant patients were randomly matched 2:1 with the allotransplant patients for age +/- 5 years, disease status at BMT, disease histology, and year of BMT. In the matched comparison, survival did not differ (relative risk of death after allotransplant: 0.711 (95% CI: 0.309-1.637)). Relapse rate was significantly lower in the allotransplant group (relative risk of relapse for allotransplant: 0.190 (95% CI: 0.043-0.834)) and treatment-related mortality was not significantly different (relative risk for allotransplant: 1.425 (95% CI: 0.527-3.851)). In conclusion, a review of a provincial strategy for treatment of NHL, shows that survival is not different after allogeneic or autologous BMT, but the rate of relapse is lower after allotransplant. These data support continuing the current provincial strategy.     

Factors associated with survival in patients with progressive disease following autologous transplant for lymphoma

Our objectives were to assess survival and predictors for survival among lymphoma patients whose disease had progressed after autologous bone marrow (ABMT) or stem cell transplantation (ASCT). Patients transplanted at Hadassah University Hospital between October 1983 and February 1999 were included. We compared survival of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) after relapse or progression. Predictors for survival were assessed in a multivariate model. Of 88 transplanted patients with HD and 152 with NHL, relapse/progression occurred in 27 (31%) and 75 (49%), respectively. Median survival postrelapse was 25 months for HD and 7.5 months for NHL (P=0.12). Seven relapsed patients with HD (26%) and 10 (13%) with NHL survived >4 years. In NHL, longer postrelapse survival was associated with indolent histologies (P=0.007). On multivariate analysis, factors associated with survival included attainment of remission postrelapse (for both diseases), use of prophylactic immunotherapy (for HD), LDH level and time from transplant to relapse (for NHL). The short-term prognosis for patients with disease progression postautologous transplant may be somewhat better for HD compared to NHL. Long-term survival is poor in both diseases. However, the survival times in the current study are twice as long as those previously reported. Treatment regimens with the potential for achieving remission may have an impact on survival.     

Long-term follow-up of allogeneic bone marrow transplantation in patients with poor prognosis non-Hodgkin's lymphoma

Relapsed or very aggressive high-grade NHL and refractory low-grade NHL have a poor clinical outcome. Autologous BMT may be used but is of limited efficacy in these cases. Allogeneic BMT offers the advantage of tumour-free bone marrow and a possible GVL effect. Between 1987 and 1996, 13 patients (median age 31 years) suffering from lymphoid malignancies underwent allo-BMT. Four patients had low-grade NHL, three intermediate-grade and six high-grade NHL. Three patients were grafted with evolutive disease, four were in partial remission after several courses of chemotherapy, two were in CR2 and four were in CR1 after initial therapy. The mean number of prior treatments was 2.7 (1-6). Median time from diagnosis to BMT was 25 months (4-90). The conditioning regimen consisted of cyclophosphamide (120 mg/kg/day for all, plus VP16 in one case) and total body irradiation. Five out of the seven patients who were not in CR at the time of transplantation entered CR after BMT. Eight patients developed acute GVHD grade > or = II and four had chronic GVHD. Nine patients are alive, eight in CR with a median follow-up of 49.8 months post BMT (2-125). Overall survival is 67.3% and the median time for EFS is 102 months. Two patients with low-grade NHL relapsed 61 and 102 months post BMT and were treated with DLI. One patient with a stage IV SLL had a partial remission and one with multiple cutaneous localisation of FL entered CR after grade IV acute GVHD. Allo-BMT is a highly effective treatment for advanced poor prognosis lymphoid malignancies with acceptable toxicity. Moreover, DLI can be effective in relapsing patients.     

Allogeneic bone marrow transplantation for infants with acute leukemia or myelodysplastic syndrome

The objective of this study is to investigate the outcome of children 24 months of age or younger (infants) at the time of allogeneic bone marrow transplantation (BMT) for acute leukemia or myelodysplasia. We analyzed the survival rate, prognostic factors, incidences of late sequelae, and immune reconstitution in 22 infants who underwent allogeneic BMT. The 5-year event-free survival estimate was 45.5% (95% confidence interval (CI), 24.4% to 63.3%). Six patients died of transplant-related complications and six died of disease relapse. Remission status at the time of BMT was the most important prognostic factor (P = 0.005): no patient who received a transplant while their disease was not in remission survived, whereas the 5-year survival estimate for infants who underwent BMT during remission was 56% (95% CI, 31% to 75%). Long-term outcomes in the 10 infant survivors were compared with those of 10 older controls matched for diagnosis, disease status at the time of BMT, calendar year at the time of BMT, and source of stem cells. Immune function 1 year after transplantation and the incidences and spectra of late sequelae were similar for both groups during a median of 3.5 years (range, 1.5 to 7.2 years) of follow-up.     

Marrow transplantation for non-Hodgkin's lymphoma: a multi-centre study from the European Co-operative Bone Marrow Transplant Group

Twenty-five patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) were treated by allogeneic bone marrow transplantation. For the nine patients transplanted in first complete remission the disease-free survival was 100%; of the nine patients transplanted in subsequent remissions four (44%) achieved long-term disease-free survival but two died of relapsed lymphoma. For the seven patients transplanted at a time when they had active disease, the initial complete remission rate was high but four died of progressive lymphoma and no patient achieved long-term disease-free survival. The incidence of complications associated with allogeneic bone marrow transplantation was similar to that observed in other series of patients transplanted for haematological malignancy and was related to the status of the disease at the time of transplant. Thus allogeneic bone marrow transplantation is a radical but effective treatment for patients with NHL who have 'minimal residual disease'. Efforts to define further the subset of patients who can most successfully be treated by transplantation may improve the overall results.     

Factors affecting the outcome of allogeneic bone marrow transplantation for adult patients with refractory or relapsed acute leukaemia

We evaluated the outcome of allogeneic bone marrow transplantation (BMT) for advanced acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) in 383 adult patients in nine Australian adult BMT centres between 1981 and 1997. The median overall survival for the group was 4.8 months, with an estimated 5-year survival of 18%. 28% of patients died of transplant-related toxicities within the first 100 d. Progressive disease was responsible for 48% of deaths. Multi-factor analysis demonstrated that AML (v ALL), disease status (second complete remission [CR2] v others), age (< 40 years) and duration of prior first complete remission (CR1) (> 6 months) were pre-transplant variables significantly associated with improved survival. Acute graft-versus-host disease (GVHD) of any grade reduced the rate of relapse in both AML and ALL, but only grades I-II were associated with improved survival. Both limited and extensive chronic GVHD were associated with increased survival. Only patients with AML in untreated first relapse or CR2, with a duration of CR1 > 6 months, or patients with T ALL, had a 5-year survival > 20%. Transplants for AML in induction failure or pre-B ALL in untreated first relapse or CR2 had an intermediate outcome, with 5-year survival of 10-20%. A 5-year survival of < 10% was observed for patients transplanted for ALL in induction failure or for pre-B ALL or AML in refractory first relapse or beyond CR2. These results suggest that for most adult patients with advanced acute leukaemia an allograft offers only a small chance of cure.     

Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma

We report the outcomes after reduced-intensity conditioning allogeneic stem cell transplantation (RIT) for non-Hodgkin lymphoma (NHL) in 88 patients (low-grade NHL [LG-NHL], n = 41; high-grade NHL [HG-NHL], n = 37; mantle cell lymphoma [MCL], n = 10). Thirty-seven patients had previously received autografts, and 21 were in complete remission (CR) at transplantation. Conditioning therapy consisted of alemtuzumab, fludarabine, and melphalan. Sixty-five patients received peripheral blood stem cells (PBSCs) from HLA-identical siblings, and 23 received bone marrow (BM) from matched unrelated donors. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporin A. Grade III-IV acute GVHD developed in 4 patients, and chronic GVHD developed in 6 patients. With a median follow-up of 36 months (range, 18-60 months), the actuarial overall survival (OS) rates at 3 years were 34% for HG-NHL, 60% for MCL, and 73% for LG-NHL (P < .001). The 100-day and 3-year transplant-related mortality (TRM) rates for patients with LG-NHL were 2% and 11%, respectively, and were better (P = .01) than they were for patients with HG-NHL (27% and 38%, respectively). The actuarial current progression-free survival (PFS) rate at 3 years, including the rate for patients who achieved remission after donor lymphocyte infusion (DLI) for progression, was 65% for LG-NHL, 50% for MCL, and 34% for HG-NHL (P = .002). Twenty-one patients underwent DLI for matched related donor (MD)-persistent disease or relapse, and 15 underwent DLI for mixed hematopoietic chimerism. Patients who experienced relapses of LG-NHL and chronic lymphocytic leukemia (CLL) achieved excellent PFS with extremely low TRM and GVHD, even when matched related donors were unavailable.     

Allogeneic bone marrow transplantation in patients with follicular lymphoma: a single center study

The role of allogeneic BMT for follicular lymphoma remains to be established. From 1995 to 2000, 16 patients with follicular lymphoma underwent allogeneic BMT at our center. At the time of transplantation, two patients were in complete remission, 11 in partial remission and three had refractory disease. Fourteen patients were transplanted using a standard myeloablative conditioning regimen and two a nonmyeloablative conditioning regimen. With a median follow-up of 1184 days (range 403-1999 days) after BMT, 11 patients were alive, whereas five died of transplant-related mortality. Eight patients remained in CR 284+ to 1022+ days (median 560+ days) after BMT. Two patients relapsed 63 and 1073 days after BMT. They achieved a further complete remission after salvage treatment and remained alive 403 and 1224 days after BMT, respectively. One patient with autologous reconstitution had never been in CR after BMT. He was retreated with salvage chemotherapy but only achieved CR with subsequent rituximab treatment and was still alive, 1999 days after transplantation. The estimated 2-year overall survival and event-free survival rates were 68% and 55%, respectively. Age greater than 37 years at diagnosis, positive recipient CMV serology and ECOG performance status > or =1 at diagnosis were associated with shorter overall survival (P = 0.05, P = 0.009 and P = 0.03, respectively). Ann Arbor III-IV stage at diagnosis was associated with shorter event-free survival (P < 0.04). Allogeneic BMT seems to be effective for patients with follicular lymphoma. However, the relatively high rate of early transplant-related mortality emphasizes the need to define indications and use prospective protocols involving a less toxic transplant procedure.     

Autotransplants for histologically transformed follicular non-Hodgkin's lymphoma

Histological transformation from a follicular non-Hodgkin's lymphoma (NHL) to a higher grade lymphoma carries a poor prognosis despite treatment with aggressive anthracycline-based chemotherapy. We retrospectively analysed 35 patients with histologically transformed NHL who underwent high-dose therapy and autotransplantation at our centre. Patients up to 65 years old were eligible for autotransplant at the time of transformation or with subsequent relapses, provided that chemosensitivity to a salvage regimen could be demonstrated. All patients received high-dose therapy [etoposide 60 mg/kg, melphalan 160 mg/m2 and fractionated total body irradiation (TBI) 12 Gy] followed by unpurged autologous bone marrow or blood stem cell rescue. Most patients (69%) had advanced stage disease (stages 3--4) at transformation and bone marrow involvement was common (49%). Twenty-six (74%) patients were in partial remission (PR) and nine (26%) in complete remission (CR) at the time of transplant. Median duration from transformation to transplant was 10.9 months (range, 5.2 months--4.6 years). At a median follow up of 52 months after autotransplant, 19 (54%) patients had died. Causes of death were progressive lymphoma in nine patients (26%), treatment-related mortality (TRM) in seven (20%) and myelodysplasia in three (8%). Only five patients in our cohort were > 60 years old, but all died as a result of treatment-related causes (mostly pulmonary infections). Five-year overall survival and progression-free survival from time of transplant were 37% and 36% respectively. Using multivariate analysis of factors including gender, age, stage, extranodal disease, disease bulk, B symptoms, number of prior therapies, relapse status and CR/PR status at transplant, only advanced age significantly predicted for survival from autotransplant (P = 0.002). Our survival data are comparable to previous reports of autotransplantation for transformed NHL and suggest a benefit over standard chemotherapy alone in selected patients. However, our high TRM cautions the use of aggressive therapy, including TBI, in patients over 60 years old.     

A comparative study of combination chemotherapy versus marrow transplant in first remission in adult acute lymphoblastic leukaemia

The results of conventional chemotherapy in adult acute lymphoblastic leukaemia (ALL) have not improved substantially in recent years. The present study is based on a flexible policy of marrow transplantation (allograft and autograft without marrow purging) in first remission compared with a group treated with standard maintenance therapy after a common induction sequence. The actuarial disease free survival (DFS) and actuarial overall survival (OS) at 3 years for autologous marrow grafted patients was 30% and 65% respectively. The allogeneic transplant group had DFS of 30% and OS at 3 years of 38% compared with DFS (12%) and OS (12%) for patients on 6-mercaptopurine and methotrexate maintenance. The actuarial disease free survival calculations include patients on protocol not entering remission, therefore, giving the worst possible result. We conclude that high dose chemo/radiotherapy with autologous marrow rescue in first remission followed by no maintenance provides better results in terms of overall survival and quality of life than standard ALL maintenance in adult patients. Results for allogeneic transplant in ALL are less good in terms of duration and quality of survival and the majority of deaths are related to causes other than leukaemic relapse.     

Autologous hematopoietic cell transplantation non-Hodgkin's lymphoma: 100 month follow-up

One hundred and ten adult patients with non-Hodgkin's lymphoma (NHL) received an autologous hematopoietic cell transplant (ABMT) from 1988 to 1993. All received a uniform preparative regimen of cyclophosphamide, BCNU and etoposide (CBV). Twenty-one percent had low grade histologies, 54% intermediate grade, and 25% high grade. Median follow-up of 48 survivors is 100 months. Kaplan-Meier 10 year overall survival and relapse-free survival for the entire group is 42% and 32%, respectively. Fifty patients were in complete remission 2 years post transplant. With additional follow-up, patients with high grade malignancies are cured, while patients with intermediate or low grade histologies were at continued risk of relapse up to 5 years post transplant. Of 39 patients in complete remission 5 years post transplant, none have relapsed with additional extended follow-up. We conclude that patients with NHL treated with ABMT, if in CR 5 years post transplant, are at very low risk of relapse with extended follow-up, suggesting the possibility of cure for all histologies, including those with low grade NHL.     

Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: a report from the Group d'Etudes de la Greffe de Moelle Osseuse.

From October 1987 to December 1990, 101 patients with acute myeloid leukemia (AML) were randomized to be transplanted in first complete remission (CR1). Preparative regimen including Cytoxan (120 mg/kg) with total body irradiation (CYTBI) (N = 50) or busulfan (16 mg/kg) (BUSCY) (N = 51) was followed by allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling. Mean time between diagnosis and BMT was 119 days. The outcome for CYTBI at 2 years is better for probability of disease-free survival (DFS) (72% v 47%) (P less than .01), survival (75% v 51%) (P less than .02), relapse (14% v 34%) (P less than .04), and transplant mortality (8% v 27%) (P less than .06). In multivariable analysis, higher relapse and decreased survival and DFS were associated with BUSCY regimen, while chronic graft-versus-host disease also influenced independently the probability of relapse. This demonstrates the present limitation of busulfan use in this setting, possibly due to probable individual variations in biodisponibility. Furthermore, besides the anti-leukemic effect of preparative regimens, this trial points out the progress accomplished in BMT management (transplant mortality = 8% in CYTBI) over the last 20 years as well as the effectiveness of transplant in early first CR after CYTBI (DFS = 72% at 2 years).     

Allogeneic bone marrow transplantation versus chemotherapy in the treatment of childhood acute lymphoblastic leukemia in second complete remission

Seventy-six patients between the ages of 2 and 17 years with acute lymphoblastic leukemia (ALL) achieved a second complete remission induced by polychemotherapy. Twenty-one had an HLA-identical donor and underwent allogeneic bone marrow transplantation (BMT) after conditioning with total body irradiation and cyclophosphamide. The remaining 55 patients lacked a suitable donor and received intensive chemotherapy as treatment. Fifteen patients were excluded from the analysis because they relapsed within 3 months after achieving a second complete remission. Three of the 21 BMT patients died of transplant-related complications and seven relapsed between 90 and 480 days after transplantation. Eleven patients are alive and disease free at 5.5-71 months with an actuarial survival of 47.1%; eight patients are on a plateau extending from 22 to 71 months. Thirty-three patients treated with chemotherapy died from relapse and seven are alive and disease free 7.5-99 months from the second remission, with an actuarial survival of 9%. The probability of survival was significantly higher in the BMT group (p less than 0.025). The probability of remaining in complete remission in the BMT group was 58.5% versus 10.9% in the chemotherapy group (p less than 0.005). Our results show that BMT is the best alternative therapy for children affected by ALL who have had a relapse in the marrow.