Modified chemotherapy with carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) and autologous bone marrow transplantation in 24 poor-risk patients with acute lymphoblastic leukemia.

Twenty-four poor-risk patients with acute lymphoblastic leukemia received a modified regimen of carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) followed by autologous bone marrow transplantation (ABMT). Nineteen patients were in second or subsequent complete remission (CR) when treated with this regimen; 3 died early, 2 died of pneumonia in CR, 11 relapsed within 3 months (median), and 3 remain in CR with no maintenance therapy 14-24 months after ABMT. Of the 5 patients with measurable disease who were treated, 3 had CR and 1 remains in CR without maintenance therapy more than 28 months after ABMT. The toxicity of this regimen was acceptable, but late pulmonary toxic effects remain a major concern. These results are poor in terms of efficacy, and new effective methods of eradicating acute lymphoblastic leukemia in patients with poor prognosis should be investigated.

Intensive sequential chemotherapy with repeated blood stem-cell support for untreated poor-prognosis non-Hodgkin's lymphoma.

PURPOSE: To demonstrate the feasibility and efficacy of six ambulatory high-dose sequential chemotherapy courses that include three intensified cycles supported by stem-cell infusion in high-risk and high-intermediate-risk untreated non-Hodgkin's lymphoma (NHL) patients. PATIENTS AND METHODS: A pilot nonrandomized study included 20 untreated patients aged less than 60 years with aggressive histologically identified NHL and two or three adverse-prognosis criteria (International Index). Patients received an ambulatory regimen with high-dose chemotherapy supported by granulocyte colony-stimulating factor (G-CSF) and repeated peripheral-blood stem-cell (PBSC) infusion. The median age was 39 years (range, 20 to 59), with 13 men and seven women. Chemotherapy consisted of one cycle every 21 days for a total of six cycles. The first three cycles (A1, A2, and A3) consisted of cyclophosphamide (Cy) 3,000 mg/m2, doxorubicin (Doxo) 75 mg/m2, and vincristine 2 mg (plus corticosteroids). The last three cycles (B4, B5, and B6) consisted of the same drug combination plus etoposide 300 mg/m2 and cisplatin 100 mg/m2. For an expected duration of 18 weeks, the projected dose-intensity was 25 mg/m2/wk for Doxo and 1,000 mg/m2/wk for Cy. G-CSF 300 micrograms was administered from day 6 following each cycle until neutrophil reconstitution. Two aphereses were performed at approximately day 13 after each A cycle, and PBSCs were injected at day 4 of each B cycle. Radiotherapy on tumor masses > or = 5 cm was scheduled after completion of the last cycle. RESULTS: The median duration of grade 4 neutropenia was 1 day (range, 0 to 7) for each A cycle and 4 days (range, 1 to 10) for each B cycle (P = .02). The median duration of grade 4 thrombopenia was 0 days (range, 0 to 8) for each A cycle and 6 days (range, 1 to 21) for each B cycle (P < .001). Hospitalization for febrile neutropenia was required for 18% and 44% of patients during cycles A and B, respectively (P < .01). Only three patients did not complete the protocol: one due to emergency surgery after cycle B4, one who died after cycle B5 from interstitial pneumonia, and one with delayed hematologic reconstitution after cycle B4. Chemotherapy delivery was optimal (median actual relative dose-intensity, 97%; range, 66 to 100). The median total dose administered over 18 weeks was 18,000 mg Cy (range, 12,000 to 18,000), 450 mg Doxo (range, 300 to 450), 900 mg etoposide (range, 300 to 900), and 300 mg cisplatin (range, 100 to 300). Evaluation of response after six courses showed 13 complete remissions ([CRs] 65%), four partial remissions (PRs), two nonresponses (NRs), and one toxic death. With a median follow-up period of 25 months (range, 16 to 43), 15 patients are alive, with 12 in continuous first CR; five patients relapsed (four of four PRs and one of 13 CRs). Two-year survival and failure-free survival (FFS) rates are 73% and 56%, respectively. The disease-free survival (DFS) rate for the CRs is 86%. CONCLUSION: PBSC support contributes to the feasibility of first-line, very-high-dose, ambulatory chemotherapy delivery in poor-risk NHL and is associated with a high rate of remission and FFS.

Production of ex vivo expanded hematopoietic cells and progenitors in a closed bioreactor, starting with a small volume marrow collection: A feasibility study in patients with poor-risk breast cancer and receiving high-doses of cyclophosphamide.

We report a clinical pilot study conducted in 6 women with poor-prognosis breast cancer. The goal was to evaluate the feasibility and safety of producing hematopoietic progenitors and cells from a small marrow sample, for clinical use after high-dose cyclophosphamide. A small volume marrow collection was obtained, using local anesthesia and conscious sedation, before the first of two chemotherapy cycles. Cells were cryopreserved, and later thawed to inoculate two Aastrom Biosciences Inc Replicell bioreactors, on time to reinfuse ex vivo expanded cells after the second chemotherapy cycle. Patients recovered neutrophils and platelets at similar times after the first and second chemotherapy cycles, and showed comparable clinical events. This pilot study prepares future randomized trials, designed to evaluate clinical benefits associated with the use of ex vivo expanded cells in the setting of multicycle high-dose chemotherapy.

Immune reconstitution and outcome after unrelated cord blood transplantation: a single paediatric institution experience.

We report the outcome of 12 children who underwent unrelated cord blood transplant (U-CBT) in a single institution between February 1997 and July 1998. The 1 year event-free survival was 67% (95% CI of 26%). Four children died with infectious complication as cause of death in three cases. Immune reconstitution was studied during first year post transplant by assaying total lymphocyte counts, B cells, NK cells and T cell subsets in the eight disease-free surviving patients. We observed a prompt recovery of CD19+ cell number which was greater than 500/microl at 9 months for all patients except the one with severe cGVHD. B cells constituted the predominant lymphocyte subset at 6 and 9 months post transplant with normal or elevated B cell numbers according to normal paediatric range. We noted normal serum immunoglobulin levels at 6 months post transplant for IgA and IgM and at 9 months for IgG. The CD3+ cell count and particularly the CD3+CD8+ T cell subset remained depressed until 12 months post transplant. Six months after unrelated CBT, seven out of eight patients had less than 100 CD3+CD8+ cells/microl. CD3+CD4+ cell recovery was less impaired with all children achieving an absolute count of CD3+CD4+ cells greater than 200/microl during the first year in a median of 5 months. The percentage of NK cells was elevated during the first 6 months after CBT but their absolute count remained within the normal range. Bone Marrow Transplantation (2000) 25, 53-57.

Delayed administration of granulocyte colony-stimulating factor after autologous bone marrow transplantation: effect on granulocyte recovery.

Recombinant granulocyte colony-stimulating factor (rhG-CSF) has been shown to hasten granulocyte recovery after autologous BMT. In current protocols, rhG-CSF treatment starts 1 day after BM reinfusion. Our study retrospectively examined the effects on haematological recovery of a day 6 delayed administration. Seventy-eight patients receiving autologous BMT for malignant lymphoma (21 non-Hodgkin's lymphoma and 9 Hodgkin's disease) or solid tumors (33 breast carcinoma and 5 ovarian carcinoma) were split up into three study groups. Two groups receiving a 5 micrograms/kg/day of rhG-CSF starting either 1 day (day +1 group, n = 25 patients) or 6 days (day +6 group, n = 24 patients) after BM reinfusion were compared with 29 historical control patients. Granulocyte recovery to 0.5 x 10(9)/l was 12 days in day +6 and day +1 groups versus 16 days in control group (p < 0.005) without any difference in other hematological parameters, infectious complications or length of hospitalisation between the three groups. The day +6 administration allows elimination of a median of 7 days rhG-CSF. It has been concluded that the day +6 administration gives the same clinical benefit as day +1 administration with consequent cost reductions.

Comparison of G-CSF-primed peripheral blood progenitor cells and bone marrow auto transplantation: clinical assessment and cost-effectiveness.

The introduction of hematopoietic growth factors (HGFs) offers new opportunities for autologous transplantation by facilitating and enriching collection of circulating progenitor cells from peripheral blood as a source of stem cell rescue. Substitution of peripheral blood progenitor cells (PBPC) from bone marrow in autologous transplantation for therapy in advanced cancers requires clinical and economic assessment. We carried out the first clinical and cost-effectiveness study in an experimental group of 16 patients autografted with PBPC primed by G-CSF alone and with G-CSF stimulation post-transplantation, comparing these with two other groups of 17 and 21 patients who received autologous bone marrow transplantation with and without G-CSF stimulation, respectively, post-transplantation. We confirmed the ability of primed PBPC to achieve durable engraftment in a shorter time than classical BMT (median number of days to reach 0.5 x 10(9)/l neutrophils = 10.5 versus 12 and 16, respectively) to improve overall hematological recovery (median number of days to recover a platelet count > or = 25 x 10(9)/l, independent of platelet transfusion = 14.5 vs 23 and 20) and to shorten length of hospitalization. Total costs of PBPC autografting remain lower than those of autologous BMT either with or without G-CSF, and cost-effectiveness ratios using hematological recovery end points are in favour of PBPC. Finally, PBPC is a safe and effective way of performing dose-intensification in cancer patients, although further improvements are required to optimize the procedure and so further decrease the costs.

Comparison of anxiety, pain and discomfort in two procedures of hematopoietic stem cell collection: leukacytapheresis and bone marrow harvest.

The aim of this study was to compare anxiety, pain and discomfort of cancer patients submitted to either peripheral blood progenitor cell collection (PBPCC) or bone marrow harvest (BMH). Patients, randomized (7/1993-2/1994), in view of autograft, to receive the first procedure or the second one, completed self-administered questionnaires. Anxiety was assessed by the State Trait Anxiety Inventory and pain using visual analogical scale (VAS) and McGill Pain questionnaire. Before the procedure, BMH patients (n = 25) experienced more anxiety (P < 0.01) and more trouble or inconvenience for having to come and stay at the hospital (P < 0.0001) than PBPCC patients (n = 40). Pain due to BMH is significantly higher than pain induced by PBPCC (P < 0.001 for VAS and total McGill score). However, patients submitted to PBPCC with a femoral catheter (n = 19) had significantly higher total McGill scores and sensory sub-scores than patients without it (n = 21). At discharge from the hospital, PBPCC patients expressed more positive judgements towards the collection procedure than BMH patients. These results suggest that a better patient acceptability of high-dose chemotherapy followed by autograft may be obtained by substituting PBPCC for BMH for stem cell collection.

Repeated courses of high dose melphalan and unpurged autologous bone marrow transplantation in children with acute non-lymphoblastic leukemia in first complete remission.

Eleven children between the ages of 1 and 16 years with acute non-lymphoblastic leukemia (ANLL) in first remission were included in a study of double unpurged autologous bone marrow transplantation (ABMT). Prior to each ABMT patients received massive chemotherapy with melphalan at a dosage of 140 mg/m2. The first ABMT was done within a median of 4 months after the achievement of complete remission. As soon as the children had adequate hematologic recovery, a second marrow collection was done, followed by a second course of melphalan and a second ABMT. The duration of aplasia was significantly longer after the second ABMT than after the first, but the non-hematologic toxicity was relatively mild in each case and no patient died from the procedure. Four patients relapsed and seven are alive in unmaintained complete remission with a median duration of leukemia-free survival of 29 months (range 15-56 months) after the first ABMT. These data demonstrate the feasibility of repeating ABMT after melphalan in children with ANLL. The eventual impact of such therapy needs to be demonstrated in prospective randomized studies.

Phase I study of in vivo lenograstim (rHuG-CSF) for stem cell collection demonstrates improved neutrophil recovery after autologous bone marrow transplantation.

Colony stimulating factors and especially rHuG-GSF, the first available neutrophil growth factor, have led to considerable interest in the field of stem cell transplantation because of their ability to induce stem cell peripheralization either alone or in association with high-dose chemotherapy. Few data exist, however, on the impact of rHuG-CSF on large scale bone marrow collection and autologous bone marrow transplantation (ABMT). This phase I, non-randomized, dose escalation study of rHu-G-CSF (lenograstim) administered to 30 patients at doses ranging from 1 to 40 micrograms/kg/day for 5 days before bone marrow harvesting showed that priming with rHu-G-CSF in vivo increased the number of bone marrow cells and D14 myeloid restricted progenitors (CFU-GM) and led to a better neutrophil recovery after ABMT compared with a contemporary unprimed control population. Otherwise, this study established that 5 days of rHuG-CSF therapy, as a sole stimulus, induced a tenfold increase in the circulating CFU-GM amongst which immature progenitors, estimated by the Delta assay (secondary CFU-GM grown after 7 days of liquid culture/primary CFU-GM), are detected. These conclusions were valid for doses as low as 2 micrograms/kg/day which induced only mild neutrophilia up to the highest dose (40 micrograms/kg/day) and suggest that a short course of rHuG-CSF is beneficial in increasing the stem cell collection.

Administration of G-CSF can be delayed after transplantation of autologous G-CSF-primed blood stem cells: a randomized study.

Hematopoietic growth factors like G-CSF or GM-CSF have been shown to shorten the period of severe neutropenia after HD chemotherapy and autologous BMT, and are now widely used to mobilize hemopoietic stem cells into peripheral blood. In order to evaluate the possibility of delaying G-CSF administration after transplantation of G-CSF mobilized blood stem cells (BSC), we randomized 35 cancer patients to receive CSF at day 1 (group 1, n = 19) or at day 6 (group 2, n = 16) after transplantation and here we present their hematological reconstitution. BSC collection was performed by apheresis after G-CSF priming for 5 or 6 days (600 micrograms daily subcutaneously). Hematological recovery is comparable between the two groups: a median of 10 (range 7-16) vs 11 (range 9-18) days to reach an ANC > 0.5 x 10(9)/1 in group 1 (G-CSF day 1 after transplant) vs group 2 (G-CSF day 6 after transplant, P = NS). Median time to reach an unsupported platelet count of 25 x 10(9)/1 was 14 days in the two groups (range 8-110 and 10-40 respectively, P = NS); patients received less G-CSF after transplantation in group 2. No difference appeared in terms of transfusion support, number of days of fever of i.v. antibiotic treatment. Patients' hospital stay was the same in the two groups. Our data suggest that delaying G-CSF administration after infusion of mobilized blood cells is not detrimental to hematological recovery, while it lowers the overall cost of the procedure.

Autologous bone marrow transplantation for B cell malignancies after in vitro purging with floating immunobeads.

We report here 16 autologous bone marrow transplantations (ABMT) for poor prognosis B or pre-B malignancies (16 acute lymphoblastic leukemias (ALL), three Burkitt lymphomas, one multiple myeloma) in 11 adults and five children where in vitro purging was accomplished by means of floating immunobeads. This method was developed to avoid non-specific killing by complement or toxin or batch-to-batch variability and provides a 3 log reduction of tumor in a model of B lymphoid malignancies. Low density bone marrow mononuclear cells were incubated for 30 min at 4 degrees C with anti CD10 (ALB2 Immunotech) and/or anti CD19 (Bg4) monoclonal antibodies (MoAb) and then mixed with low density polypropylene beads precoated with a rat antimouse MoAb. After 1 h at 4 degrees C the beads with target cells were decanted; the depleted marrow was collected through a microfilter and cryoperserved. After immunodepletion the recovery of nucleated cells was 75% with a median of 0.75 x 10(8) cells/kg (range 0.3-3.6) and the recovery of hematopoietic progenitors was 83% with a median of 2.9 x 10(4) CFU-GM/kg. The conditioning regimen consisted of busulfan 16 mg/kg and melphalan 140 mg/m2 for three patients, fractionated total body irradiation (TBI) following melphalan 140 mg/m2 for nine patients, TBI and cyclophosphamide 120 mg/m2 for two patients and TBI associated with melphalan and cyclophosphamide for two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Allogeneic or autologous bone marrow transplantation for acute lymphoblastic leukemia in first complete remission.

Forty-seven patients with high risk acute lymphoblastic leukemia (ALL) received an allogeneic (allo) or autologous (auto) bone marrow transplant (BMT). Patients in both groups were comparable in terms of age, initial presentation of ALL and induction chemotherapy. Allo patients were transplanted earlier (median 3 months after CR) than auto patients (median 6.5 months after CR). Auto patients received more consolidation chemotherapy before BMT. All patients received total body irradiation 2.2 Gy/day x 5 days after cyclophosphamide 60 mg/kg x 2 (18 allo and five auto) or melphalan 140 mg/m2 (seven allo and 17 auto). Prevention of graft-versus-host disease (GVHD) was by conventional immunosuppression in 17 patients and T cell depletion in eight. Seven patients (28%) developed moderate to severe acute GVHD. Auto marrow was treated in vitro in each case. Seven patients died in CR from BMT complications (five allo and two auto). The probability of relapse was 9% for patients receiving allo BMT and 52% for patients receiving auto BMT (p less than 0.01). The disease-free survival was 71% for allo BMT and 40% for auto BMT (p = NS). Early BMT is an effective form of consolidation for high risk patients with ALL in first CR. An allogeneic anti-leukemia effect was demonstrated in this study.

Clinical and economic comparison of lenograstim-primed blood cells (BC) and bone marrow (BM) allogeneic transplantation.

The study presented is a clinical and economic comparison of bone marrow (BM) and blood cells (BC) allogeneic transplantation. We performed a case-control study to compare 17 patients receiving allogeneic BC transplant in a pilot study to an historical group of 17 patients allografted with BM. We evaluated the clinical outcomes and the direct medical costs of transplantation from conditioning regimen until day 100 by detailed observation of patients' medical records. Patients in the BC group received a median of 8 x 10(6)/kg CD34+ cells (1.58-29.1) and 266 x 10(6)/kg CD3+ cells (128-469). All patients had neutrophil engraftment with a median of 14 days in the BC group vs 19 days in the BM group (P < 0.05). The Kaplan-Meier estimation of the median number of days to a platelet count of > 25 x 10(9)/l, independent of platelet transfusion, was significantly shorter in the BC group (15 (9-74)) compared with the BM group (25 (15-45)). Acute graft-versus-host disease (AGVHD) of grade > or = 2 was not significantly different between the two groups. Patients treated with BC presented a US$16,134 decrease in the cost of the first 100 days (29%, P = 0.006). Our comparison suggested that platelet reconstitution and total costs were in favor of the BC group.

Intensive chemotherapy with high doses of BCNU, etoposide, cytosine arabinoside, and melphalan (BEAM) followed by autologous bone marrow transplantation: toxicity and antitumor activity in 26 patients with poor-risk malignancies.

Twenty-six patients (median age 33 years) with poor-risk malignancies were treated with high-dose combination chemotherapy associating BCNU-etoposide-cytosine arabinoside and melphalan (BEAM) followed by autologous bone marrow transplantation (ABMT). Twenty-one patients had malignant lymphomas, three, acute lymphoblastic leukemia (ALL), and two, malignant thymomas. Eleven patients (group 1) were not in complete remission (CR) at the time of BEAM, and fifteen patients (group 2) were in CR. Hematological recovery occurred in all patients. The duration of aplasia and the non-hematological toxicities were similar in both groups. Ten of the eleven patients (group 1) evaluable for response achieved CR and one achieved partial remission (PR). Five patients relapsed, and five are in continuous CR with a short follow-up (median 8 months). Among the fifteen patients in CR at the time of BEAM (group 2), four patients relapsed and ten patients are in unmaintained continuous CR with a median follow-up of 15 months (one patient died in CR). The disease-free survival is 53%, with 29% for patients receiving BEAM while in relapse (group 1) and 65% for patients receiving BEAM while in CR (group 2). These data indicate that BEAM followed by ABMT can produce a high antitumor response with an acceptable toxicity in patients with poor-risk malignancies.

High-dose melphalan and autologous bone marrow transplant for relapsed acute leukaemia.

Seven patients with relapsed acute leukaemia were treated with high-dose melphalan (HDM) followed by the infusion of autologous cryopreserved remission marrow. Toxicity was minimal and all seven patients had a complete response. Four patients are still in unmaintained remission at 14, 13, 10, and 3 months, the first two having received a second course of HDM to consolidate the result. The role of HDM as a form of intensification therapy for patients with acute myeloid leukaemia in first remission should be investigated.

Phase-I-II study of high-dose melphalan and autologous marrow transplantation in adult patients with poor-risk non-Hodgkin's lymphomas.

Eleven adult patients with poor-risk non-Hodgkin's lymphoma were treated with high-dose melphalan (140 mg/m2) or high-dose combination chemotherapy (BCNU, Ara-C, vindesine and melphalan) followed by autologous bone marrow transplantation. Six of the eight patients evaluable for response achieved complete remission and one achieved partial remission. Response duration ranged from 1.5 to 12 months (median 2 months). Prompt hematological recovery occurred in all patients. The duration of aplasia and the extrahematological toxicity were similar in both groups. High-dose melphalan alone or associated with other drugs followed by marrow infusion appears to produce a high response rate and demonstrates the potential for salvaging patients with refractory lymphoma.

Interleukin-2 induces chemotactic deficiency in patients with onco hematologic malignancies and autologous bone marrow transplantation.

Unusual gram positive bacteremia has been reported in non granulopenic patients receiving recombinant human interleukin-2 (IL-2) suggesting a beneficial effect of anti gram positive prophylaxis in such patients. We report here studies on granulocyte functions examined during the course of high dose IL-2 therapy (16 to 24 million IU/m2/days for 11 to 18 days) administered during a period of 35 days in 14 patients including 4 solid tumors, 5 chronic myeloid leukemias, 4 recipients of autologous bone marrow transplant (ABMT) and 1 recipient of syngeneic bone marrow transplant. Neutrophils functions were studied before IL-2 administration (d 0), after the first cycle (d 8) and after the third cycle (d 36). Nylon fiber adherence, superoxide production, random migration, phagocytosis, nitroblue tetrazolium reduction, lysozyme and elastase release were not impaired significantly throughout therapy. However N-Formyl-Methionyl-Leucyl-Phenylalanine (FMLP) stimulated chemotaxis of granulocytes, normal before therapy, was significantly impaired as early at d 8 and severely inhibited at d 36 (p less than 0.001). Three septicemia, one corynebacteria parvum septicemia and two gram-negative septicemia despite normal neutrophil counts and oxacillin or Penicillin G plus Pefloxacin prophylaxis, occurred among the 14 patients studied. Although neutrophil functions were not more depressed in transplanted patients than in the other non transplanted patients, special attention should be paid to such patients in whom delayed immune reconstitution could increase the risk of sepsis.

Benefits of granulocyte-colony-stimulating factor after stem cell transfusion in intensive sequential chemotherapy for breast cancer.

The aim of this study was to evaluate the clinical and economic benefit of filgrastim given with intensive sequential chemotherapy. Women with poor-prognosis breast cancer received four cycles of high-dose cyclophosphamide (3 g/m2) and doxorubicin (75 mg/m2), followed by filgrastim 5 microg/kg/dy, stem cell collection after the cycle 1, and stem cell infusion after cycle 3 and cycle 4. The first cohort received filgrastim after the fourth cycle but the second cohort did not.Thirty three patients were included in the first cohort and 13 in the second. The results indicate that the duration of grade IV neutropenia was shorter in the group given filgrastim as was the median time to recover an absolute neutrophil count (ANC) > 1.0 x 10(9)/L. The rate and duration of the rehospitalizations were higher in the group not receiving filgrastim. We found that costs such as drugs and hospitalizations were significantly higher (p = 0.032 and p = 0.049) in the non-filgrastim-treated group. Using ANC > 1.0 x 10(9)/L as an intermediary efficiency criterion it was more cost effective to give filgrastim. It can be concluded from this study that filgrastim can decrease the duration of grade IV neutropenia in patients receiving intensive sequential chemotherapy. This, in turn, reduces the cost of hospitalization. However, in our study, this reduction of neutropenia did not have any impact on further therapy.

Outpatient sequential high dose alkylation with stem cell support for patients with advanced breast cancer: a phase I-II study.

We evaluated the feasibility of administering, in an out-patient setting, a sequential high dose alkylating regimen with hematopoietic growth factor (HGF) and stem cell support to patients with advanced breast cancer. Peripheral blood stem cells (PBSC) were previously collected after chemotherapy and HGF. Two consecutive cycles of alkylating agents were planned: Thiotepa (T) then, 15 days later, BCNU (B). Three dose levels of each agent were administered in cohorts of consecutive patients: 400, 500 and 600 mg/m2 respectively. HGF and reinfusion of PBSC followed both cycles. Toxicity and response were evaluated according to the WHO recommendations. From April 1996 to August 1988, 30 women were enrolled: 8 in the first, 12 in the second and 10 in the third dose level. In all cases, B was administered after T with a median delay of 25 days because of grade 3/4 hematological toxicity. 4 patients did not receive B because of previous lung radiotherapy, persistent tricytopenia or insufficient PBSC collection. 19 patients with measurable lesions were considered for response. The objective response rate was 48% (11% CR, 37% PR). We recommended T and B at a dose of 600 mg/m2 to conduct a phase II study in metastatic breast cancer and even to administer B before T.

Growth potential of aortic autografts and allografts: effects of cryopreservation and immunosuppression in an experimental model.

OBJECTIVE: An animal model has been used to evaluate the potential of growth of vascular autografts and allografts, and the effects of cryopreservation, rejection and immunosuppression on this growth. METHODS: In 35 animals (seven groups of five female NZW rabbits; age 5-6 weeks; weight 1.1 kg), a graft interposition was performed at the level of the infrarenal aorta. Different groups included fresh autografts, fresh and cryopreserved consanguineous allografts (donor: litter sister), fresh and cryopreserved immunosuppressed (IS) consanguineous allografts (receiving cyclosporin 10 mg/kg per day) and fresh and cryopreserved allografts. Animals were allowed to grow normally and were sacrificed at the mean weight of 2.89 kg. We studied the growth of the native aorta and of the graft and calculated the growth ratio (growth of the graft/growth of native vessel). Grafts and adjacent aorta were histologically studied. RESULTS: Growth of the graft was normal (mean ratio 1.08; S.D. = 0.21) for autografts, and for fresh and cryopreserved IS consanguineous grafts. Growth was absent (mean ratio 0.12; S.D. = 0.15) for fresh and cryopreserved allografts (P = 0.0001). In consanguineous grafts without IS, growth was absent or normal, presumably according to genetic compatibility, but never intermediate. Histological study showed normal optic microscopic aspects when growth was normal and, when growth was absent, aspects compatible with rejection including mainly intimal hyperplasia and medial thinning. CONCLUSIONS: (1) Normal growth of arterial autografts was confirmed; (2) cryopreservation did not prevent potential growth of an arterial graft; and (3) in an allogenic situation, without IS, an aortic graft, fresh or cryopreserved, never showed any growth potential.