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BACKGROUND: RBCT (RBCT) requirements of stem cell transplant (SCT) recipients are often substantial and may be related to transplant type. STUDY DESIGN AND METHODS: An analysis was done of RBCT requirements and Hb recovery kinetic in the first 60 days after HLA-identical sibling allogeneic SCT in a series of 110 consecutive patients treated for various malignant diagnoses. Patients were prepared with either an antithymocyte globulin (ATG) and reduced intensity chemotherapy-based conditioning (RIC) (n = 64) or a myeloablative conditioning regimens (MAC; n = 46). Patients received marrow (n = 64) or PBPCs (n = 46). RESULTS: Overall, intensity of conditioning regimen (RIC vs. MAC; p = 0.0005) and graft source (PBPC vs. marrow; p < 0.0001) independently predicted RBCT requirements. Hb recovery was accelerated after RIC when compared to MAC allo-SCT (p = 0.02). In RIC patients, RBCTs were inversely correlated to Hb level before conditioning (p < 0.0001) and the dose of ATG (p = 0.009). Moreover, Hb level before allo-SCT significantly influenced Hb recovery kinetic after RIC but had no impact on RBCT requirements and Hb recovery after MAC. CONCLUSION: Thus, RIC conditioning creates a different pattern of erythropoiesis recovery as compared to a MAC regimen and suggest a need for studies aimed at further reducing RBCT and accelerating Hb recovery.

Summary Objective To describe the outcome of an unselected large series of patients with lymphoblastic lymphoma (LBL) treated in a single institution. Patients and methods Sixty-two patients were treated between 1980 and 1992. Induction chemotherapy (CT) to achieve complete response (CR) was: French Multicenter Acute Lymphoblastic Leukemia (ALL) protocols (38), non-Hodgkin’s Lymphoma (NHL) protocols (20). Thirty patients underwent transplant after achieving CR (allogeneic 12; autologous 18). Results Forty-six patients (74%) achieved CR and 16 (26%) failed to respond. The patients who received an ALL induction had an 89% CR rate, while the CR rate was 52% in patients who received a NHL-like regimen. With a median follow-up of 93 months (range 36–187), the actuarial overall survival (OS) rate for all patients is 49% at five years and 41% at 10 years, and the actuarial event-free survival (EFS) rate is 45% and 37%. OS and EFS in the grafted population are, respectively, 60% and 56% at five years. Our results also show a trend toward a longer OS in allografted group. Conclusions ALL induction therapy is more effective than the NHL-like regimen for augmenting the CR rate. Autologous or allogeneic transplantation should be considered as consolidation therapy in high-risk group patients.

The reconstitution of the plasmacytoid dendritic cells (PDCs) compartment might influence outcome after allogeneic stem cell transplantation (allo-SCT). Thus, we investigated the impact of blood PDCs measured at the third month after reduced-intensity conditioning (RIC) in 54 patients who received an HLA-identical sibling allo-SCT. The absence of grade II-IV acute graft-versus-host-disease (GVHD) was associated with an improved PDC count at 3 months after RIC-allo-SCT (P=0.003; OR=6.4; 95% CI, 1.9-22). The CD34+ stem cell dose and other lymphoid subsets infused with the allograft did not affect PDC recovery. Although PDC count could not predict death from progression or relapse, patients with a "high" PDC recovery profile had an improved overall survival (OS; P=0.03), in contrast to patients with a "low" PDC recovery profile who had an increased incidence of nonrelapse mortality (GVHD, infections) (P=0.03). The overall incidence of late infections (viral, fungal and bacterial) was significantly higher in the "low" PDC recovery group as compared to the "high" PDC recovery group (59 vs 19%; P=0.002). In a multivariate analysis, only a "high" PDC count was significantly predictive of a decreased risk of death (P=0.04; RR=0.34; 95% CI, 0.12-0.96). Monitoring of PDCs at 3 months after RIC-allo-SCT may be a useful indicator predictor of long-term outcome.

Background: Aggressive non-Hodgkin's lymphomas (NHL) in patients under the age of 60 have a very poor prognosis when the international prognostic index (IPI) is high, with an age-adjusted (Aa)-IPI score at 3. In such patients, conventional chemotherapy results in a low complete response (CR) rate of 46%, a five-year survival and disease-free survival (DFS) of 32% and 58%, respectively. For this report we have analyzed whether front-line high-dose chemotherapy could influence the outcome of this group of patients. Patients and methods: From 1992 onwards we conducted two pilot clinical trials of intensive sequential chemotherapy ( ISC) with growth factors and blood stem cell support as initial treatment in 62 poor-risk patients with aggressive NHL. Of these patients, 33 were considered to be a high-risk group based on the Aa-IPI. Results: The median age was 42 years (range 21-60). The treatment was completed in 88% of patients, 86% receiving greater than 75% or more of the projected dose-intensity. Twenty patients (61%) achieved a CR. At a median follow-up of 48 months (range 26-86), the estimated five-year survival and DFS was 51% (95% confidence interval (CI): 34%-68%) and 70% (95% CI: 50%-90%), respectively. Conclusion: These results suggest that primary treatment using high-dose therapy supported by both growth factors and peripheral blood stem cells can cure up to 50% of high-risk patients with malignant lymphomas.

Allogeneic BMT for patients with acute myeloid leukemia (AML) is presently a reference therapy. The indications for this therapy may likely rely upon prognostic factors, and their importance are constantly investigated. To examine the impact of time from diagnosis to transplant on survival and Leukemia Free Survival (LFS), we analyzed 109 patients from the data base of the SFGM, patients who all had received an HLA-identical allogeneic BMT for a diagnosis of AML in First Complete Remission (CR1) between January 1987 and December 1992. All patients were prepared with cyclophosphamide (Cy) and Total Body Irradiation (TBI) (Cy — TBI), and Methotrexate (MTX) + Cyclosporine A (CSA) was used as Graft-vs.-Host Disease (GVHD) prophylaxis. Eleven patients needed 2 courses of induction to achieve CR. Time between diagnosis and BMT was 120 (64–287) days. Forty nine patients developed a grade 2 acute GVHD (Actuarial probability = 46%). With a median follow-up of 52 months (30–100), the 5 year probabilities for transplant related mortality (TRM), relapse, overall survival and LFS are respectively 25, 26, 59%, and 55%. A multivariate analysis showed that survival is adversely influenced by 3 independent factors: time to transplant (>120 days vs.≤120 days), acute GVHD (grade 2–4 vs. grade 0–1) and age (>33 vs.≤33). LFS is influenced by only the first two of these factors. The favorable impact of less time from diagnosis to transplant should lead to proceeding to the transplant as soon as possible. Practically speaking, this means that when such therapy is chosen for a patient with CR1 AML, the search for an allogeneic donor should be immediately investigated and transplant performed as soon as possible.

Increasing numbers of patients are surviving after allogeneic bone marrow transplantation and are therefore at risk for developing late complications. Among these complications, avascular necrosis of bone has been reported, but only two single-centre studies included sufficient patients to enable analysis of the risk factors for developing avascular necrosis. In this multicentre retrospective study the aim was to assess risk factors for this complication in a large number of patients. The population consisted of 4388 patients, recorded in the Societe Francaise de Greffe de Moelle (SFGM) data base, who had undergone a single allogeneic bone marrow transplant between January 1974 and December 1993. 77 patients developed avascular necrosis leading to a 4.3% projected incidence at 5 years. Symptoms developed 2-132 months after transplantation. In these 77 patients a mean of 1.87 joints per patient were affected (range 1-7). The hip joint was the most often affected (88% of patients) and 48% of the patients required joint replacement. All but two patients received steroids for acute and/or chronic graft-versus-host disease (GvHD) over a mean period of 15 months. In univariate analysis, among eight factors tested as risk factors for developing avascular necrosis, six were shown to be linked to an increased risk: older age, diagnosis of aplastic anaemia or acute leukaemia, an irradiation-based conditioning regimen, type of GvHD prophylaxis regimens, acute and chronic GvHD. In multivariate logistic regression analysis, five factors remained significantly associated with an increased risk for developing avascular necrosis: chronic GvHD (odds ratio (OR) 3.52), acute GvHD (OR 3.73), age > 16 years (OR 5.81), aplastic anaemia (OR 3.90), and acute leukaemia (OR 1.72). Avascular necrosis is not a rare late complication of allogeneic bone marrow transplantation causing significant morbidity. In this study, older age, initial diagnosis, and GvHD and/or its treatment with steroids emerged as significant risk factors.