Allogeneic bone marrow transplantation in chronic lymphocytic leukemia: 17 cases. Report from the EBMTG

Allogeneic bone marrow transplantation (BMT) was performed in 17 patients with chronic lymphocytic leukemia (CLL): 15 resistant and two untreated forms. There were 12 males and five females with a mean age of 40 years (32-49). The conditioning regimens and graft-versus-host disease (GVHD) prophylaxis varied. Successful engraftment was obtained in 15 evaluable cases. Lymphocytosis and clinical symptoms subsided in all but one case. All 15 evaluable patients developed acute GVHD. Among the 17 patients grafted, one early death was observed at the 15th day post-BMT, and one refractory patient died 2 months after BMT. Of the remaining 15 patients in complete remission (CR), four died from GVHD, hemorrhage and graft failure, and two relapsed at 7 and 54 months after BMT and died. Nine patients are alive in CR with a mean follow-up of 25.6 months (4-48). Chimerism was complete in eight patients and partial in the two T cell-depleted cases. In one case, an immunoglobulin gene rearrangement study showed no residual disease. These results suggest that allogenic BMT might be an alternative and possible curative therapy for refractory CLL in young patients when performed relatively early in the disease.     

Définition et évolution du statut nutritionnel au cours d'une greffe osseuse allogénique (15 malades): Rôle de la nutrition parentérale et de l'apport azoté

Our work concerned 15 patients (9 males, 6 females) with a mean age of 29.5 years, having a hematologic malignant disease and undergoing allogenic bone marrow transplantation.We studied :

1. The metabolic disorders induced by the conditioning regimen (chemotherapy and total body irradiation) pregraft accompanying cytolysis (day −7, −5, −2).

2. The corrective effect of a total parenteral nutrition introduced 2 days before the transplantation and pursued during 30 days post-graft (day −2 to day 30).

3. The interest of a high calorie intake (BEE × 2) and, after randomisation, of a variable nitrogen intake (24% of the total calorie intake for group A [8 patients] and 14% for group B [7 patients]). The patient characteristics of these two groups were closely comparable. Urinary parameters were studied daily (3-methylhistidine, cratinine, nitrogen) and blood parameters weekly (transferrin, pre-albumin, albumin, retinol binding protein).

We observed globally :

-- An excellent result of the nutritional support without significant weight loss;

-- protein catabolism stopped with a recovery of synthesis of RBP after day 7 and pre-albumin from day 7;

-- a decrease in muscle catabolism.

The randomized study showed :

-- a significant difference in nitrogen excretion between group A and group B;

-- earlier and better protein synthesis recovery in group A, particularly with regard to RBP and pre-albumin.

In conclusion, we recommend for the patients undergoing bone marrow transplantation :

-- nutritional support should be introduced before the conditioning regimen;

-- a high calorie intake (BEE × 2) with a nitrogen intake between 14% and 24% of the total calorie intake;

-- cyclic parenteral nutrition should be pursued during the second and third month post-graft.

Deep candidiasis in agranulocytic patients: mycological and serological surveillance in 91 febrile episodes and management of an antifungal and antibacterial protocol

This study took place between February 1984 and February 1985 in 76 febrile neutropenic patients. We evaluated the whole mycological and serological results, in 91 febrile episodes. We separated two groups: group I (acute leukemia, chronic myelo?d leukemia, medullar aplasia, lymphomas) and group II (chronic lympho?d leukemia, Hodgkin disease, myelomas, solid tumors). Patients were included in this study if they developed a temperature of 38.5 degrees C or greater and if they had less than five hundred neutrophils per mm3. They were treated with mono or bi-antibiotherapy. If the patient remained febrile more than 72 hours, an antifungal therapy was added (Amphotericin B IV). Through these weekly results, we conclude: the high frequency of digestive tract candidiasis in such patients; disseminated candidiasis occurs only in the first group patients with fungal digestive colonization; the overall response rate in this study was 77 per cent. This underlines the interest of empiric treatment with amphotericin B IV.     

Splenectomy during chronic lymphocytic leukemia

The combination of discontinuous high-dose chlorambucil therapy with splenectomy greatly increased the prognosis of aggressive forms of chronic lymphocytic leukemia (CLL). The median survival for 43 patients was 84 months from diagnosis and 48 months from splenectomy. For 15 stages O, according to Rai classification, obtained after splenectomy, duration ranged from 3 to 105 months. The median survival of a group of patients showing "nodular splenic infiltration" was 104 months and superior to that of a group of patients showing "diffuse splenic infiltration" (72 months). In four of 15 cases studied, the peripheral blood lymphocytic clone disappeared after splenectomy.     

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

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

Allogeneic stem cell transplantation in second rather than first complete remission in selected patients with good-risk acute myeloid leukemia

Through two consecutive trials, a policy that considered allogeneic stem cell transplantation (SCT) from a sibling donor in second rather than first complete remission (CR) in selected younger patients with acute myeloid leukemia (AML) with t(8;21)/inv(16) (core binding factor (CBF) group) or a normal karyotype (NN group) was followed by Acute Leukemia French Association (ALFA) centers. The outcome of 92 of these patients in first relapse (32 CBF, 60 NN) was reviewed with the aim of validating this strategy. The presence of an FLT3 internal tandem duplication (ITD) was retrospectively assessed in 50 patients. A total of 61 patients (66%) reached a second CR. Donor availability was an independent prognostic factor for survival in the whole patient population as well as in the CBF subset, but not in NN patients, further supporting this strategy for CBF-AMLs. In NN patients, FLT3-ITD was the main bad-prognosis factor for second CR achievement and survival, leading to consider SCT earlier, at least in FLT3-ITD patients with a donor.     

Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983--93 and 1994--8 at European Group for Blood and Marrow Transplantation centres

Out of 690 allogeneic matched sibling donor transplants for multiple myeloma reported to the European Group for Blood and Marrow Transplantation (EBMT) registry, 334 were performed during the period 1983-93 (all with bone marrow) and 356 during 1994-98 [223 with bone marrow and 133 with peripheral blood stem cells (PBSCs)]. The median overall survival was 10 months for patients transplanted during the earlier time period and 50 months for patients transplanted with hone marrow during the later period. The use of PBSCs was associated with earlier engraftment but no significant survival benefit compared to bone marrow transplants during the same time period. The improvement in survival since 1994 with the result of a significant reduction in transplant-related mortality, which was 38%, 21% and 25% at 6 months and 46%, 30% and 37% at 2 years during the earlier period, and the later period with bone marrow and PBSCs respectively. Reasons for the reduced transplant-related mortality appeared to be fewer deaths owing to bacterial and fungal infections and interstitial pneumonitis, in turn a result of earlier transplantation and less prior chemotherapy. Better supportive treatment and more frequent use of cytokines may also play a role. The improvement in survival was not directly related to the increased use of PBSCs.     

Intensive chemotherapy with mitoxantrone administered as a single injection in patients with high-risk acute myeloid leukemia: results of the EMA 2000 trial

Following a dose-escalation study performed to assess the maximally tolerated dose of high-dose mitoxantrone in a single injection combined with chemotherapy, a phase II trial (EMA 2000 regimen) was performed in patients with refractory or relapsed acute myelogenous leukemia (AML) between October 2000 and December 2003. Sixty-two patients entered the study and received mitoxantrone 45 mg/m² on day 1 in combination with cytarabine and etoposide. Overall, 39 patients (63%) achieved complete remission (CR). Four patients died during remission induction, and 19 patients had resistant disease. Median time to granulocyte and platelet recovery was 34 and 39 days, respectively. The predominant non-hematologic toxicity was infection, with 53% severe infections. Thirty-three of the 39 remitters received subsequent treatment consisting of maintenance chemotherapy courses in 17 patients, allogeneic stem cell transplantation (SCT) in 7 patients, and autologous SCT in 9 patients. The median overall survival of the entire cohort was 8.1 months, with 18% at 2.5 years. EMA chemotherapy using a single injection of mitoxantrone is effective in the treatment of high-risk AML. CR proportion was significantly higher in patients with a first CR duration 6 months when compared with those from a control trial using standard-dose mitoxantrone (90 vs 70%, p=0.03).