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PubMed1996

Granulocyte-colony-stimulating factor after allogeneic and autologous bone marrow transplantation in children.

We evaluated the use of granulocyte CSF (G-CSF) after both allogeneic BMT (allo-BMT) and autologous BMT (ABMT) in children. After allo-BMT, G-CSF was used in 15 children who were compared with 20 historical controls. The ABMT patients were two sequential groups: the G-CSF group of 13 children and 11 historical controls. The patients were conditioned with different high-dose chemotherapy regimens with or without total body irradiation. G-CSF was administered at 5 micrograms/kg/day s.c. and was continued until an absolute neutrophil count (ANC) of 1,000 x 10(6)/l was reached. Following allo-BMT, G-CSF accelerated myeloid engraftment with a difference of 5 days at the ANC level of 500 x 10(6)/l (P<0.02) and 9 days at 1,000 x 10(6)/l (P<0.001). In the ABMT patients, G-CSF also accelerated myeloid engraftment. The difference between the G-CSF group and the control group was 6 days at ANC 200 (P<0.05), 11 days at ANC 500 (P<0.02) and 17 days at ANC 1,000 (P<0.005). In the ABMT patients, benefit by G-CSF was also observed in a smaller number of days with fever and days on antibiotics. We conclude that G-CSG significantly accelerated myeloid engraftment, after both allogeneic and autologous BMT in children, and also decreased the duration of febrile illness in the ABMT patients.

Adolescent↗
PubMed1996

Successful bone marrow transplantation in sensitized aplastic anemia patients using total lymphoid irradiation for conditioning: long-term follow-up.

Between June 1986 and November 1994, 22 previously transfused patients with severe aplastic anemia (SAA) were treated with high-dose cyclophosphamide (CY) (50 mg/kg over 4 consecutive days) and 7 Gy total lymphoid irradiation (TLI) in two fractions before allogeneic bone marrow transplantation (BMT) from HLA-identical sibling. Graft-versus-host-disease (GVHD) prophylaxis included the combination of methotrexate and cyclosporine A in all cases. Actuarial survival at 5 years is 73 +/- 9 per cent for the entire group and 86 +/- 13 per cent for the seven patients < or = 18 years. The incidence of graft failure was 0 per cent, and of acute GVHD and chronic GVHD was 31.5 per cent and 24 per cent respectively. Prolonged interval from diagnosis to BMT adversely influenced survival (P = 0.03). No hypothyroidism or secondary malignancies have been documented in this series. Our findings indicate that survival with CY-TLI is comparable to that obtained using preparative regimens without radiation. The changing role of radiotherapy in pretransplant immunosuppression for SAA is discussed.

Adolescent↗
PubMed1994

Autologous bone marrow transplantation in children with advanced neuroblastoma.

BACKGROUND: Encouraging results have been reported with high dose chemotherapy and total body radiation followed by bone marrow autotransplantation in children with advanced neuroblastoma; however, relapse remains a significant problem. METHODS: The authors treated 22 children with advanced neuroblastoma with high dose chemotherapy, surgery, intraoperative radiation, and a bone marrow autotransplant (treated in vitro to remove tumor cells) followed by 13-cis-retinoic acid. RESULTS: The 3-year relapse rate was 25% (95% confidence interval [CI], 6-44%). The 3-year disease free survival rate was 72% (95% CI, 52-92%). Toxicities included hemolytic uremic syndrome, herpes infection, and hepatic venoocclusive disease. CONCLUSION: These data suggest that this treatment strategy offers an increased rate of 3-year disease free survival. The nonrandomized nature of this study and its use of multiple modalities precludes the analysis of the specific contribution of each treatment component and comparison with conventional therapy.

Bone Marrow Purging↗
PubMed1994

A radiologic syndrome after high dose chemotherapy and autologous bone marrow transplantation, with clinical and pathologic features of systemic candidiasis.

BACKGROUND: The use of high dose chemotherapy in the treatment of solid tumors is associated with prolonged neutropenia and, consequently, in some patients, systemic candidiasis. The authors describe their experience with a clinicoradiologic syndrome developing after high dose chemotherapy was administered to patients with breast cancer. METHODS: The authors evaluated the clinical and radiologic records of 12 patients in whom hepatic, splenic, or renal candidiasis developed. RESULTS: Three patients had positive blood cultures for candida tropicalis. One of these patients and two others had fungal organisms identified with special stains of an organ aspirate. Most patients were asymptomatic, and most of them were treated successfully with antifungal agents, although untreated patients also recovered. There were no fatalities due to the candidiasis. CONCLUSIONS: A radiographic syndrome resembling hepatic, splenic, or renal candidiasis is described, which occurred after high dose chemotherapy was administered and autologous bone marrow transplantation was performed on patients with breast cancer. This syndrome has a favorable prognosis. Conclusions as to the more indolent nature of this syndrome cannot be made; however, this topic warrants further investigation.

Adult↗
PubMed1995

Leukodepleted-ABO-identical blood components in the treatment of hematologic malignancies: a cost analysis.

To assess the effect of ABO-identical, filtration leukodepleted transfusions on resource consumption and costs of care we performed a cohort study in consecutive adult patients admitted for induction therapy of acute myeloid or lymphoid leukemia during 1985-92 (n = 120) and consecutive adult patients admitted for autologous bone marrow transplantation for Hodgkin's or non-Hodgkin's lymphoma during 1989-1991 in our university hospital. Patients with acute leukemia received either ABO unmatched, unfiltered transfusions (1985-89), ABO identical, unfiltered transfusions (1987-90), or ABO identical, filtered transfusions (1990-92). Patients with lymphoma received either ABO unmatched, unfiltered transfusions (1989-90) or ABO identical, filtered transfusions (1990-91). Mean platelet transfusion requirements per patient decreased with ABO identical platelets and filtered transfusions: from 143 to 71 units in the transplant setting; from 146 to 83 in acute leukemia (P < 0.05). Mean hospital ancillary service charges in 1992 dollars decreased with ABO identical platelets and filtered transfusions approximately $14,000 per patient for acute leukemia and $26,000 for for lymphoma. Per patient actual costs for filters ($643 in transplantation for lymphoma and $875 in leukemia) were offset by savings in actual blood component purchase costs alone ($4,127 in lymphoma and $3,283 in leukemia). In our setting, introduction of ABO identical platelets and filtration leukodepletion were implemented with substantial decreases in costs.

ABO Blood-Group System↗
PubMed1992

Reticulocyte quantification by flow cytometry, image analysis, and manual counting.

Reticulocyte counting by flow cytometry with thiazole orange was compared to manual or automated counting of new methylene blue stained blood smears. Forty-nine samples were compared for manual counting from randomly chosen clinical samples. Two hundred and eighty-nine samples from bone marrow transplant patients were compared during the period before and through chemo-irradiation and engraftment. The slopes of correlation plots were less than 1 when flow cytometric data were the dependent variable, suggesting that thiazole orange is less sensitive than new methylene blue. In a third study, 407 samples from bone marrow transplant patients were compared after increasing the thiazole orange concentration. The reticulocyte fluorescence distribution was divided into four groups of the brightest (youngest) 40, 60, 80, and 100% of reticulocytes. The slopes from regression analysis were 0.25, 0.49, 0.78, and 1.14, respectively. This demonstrates that thiazole orange is more sensitive than new methylene blue because the window of analysis includes an increased fraction of mature reticulocytes. In addition, the precision of each assay as measured. The rank order of precision from high to low was flow cytometry > image analysis >> manual counting.

Benzothiazoles↗
PubMedDate not supplied

Transplantation of T-lymphocyte depleted marrow with an addback of T cells.

Depletion of T-lymphocytes from allogeneic marrow prior to transplantation decreases the risk of serious graft versus host disease (GvHD), but also increases the risk of relapse. We have used a partial T-cell depletion technique, in the hope of controlling GvHD without compromising relapse risk. Allogeneic marrow was fully T-cell depleted ex vivo with Campath 1M, and infused together with an 'addback' of 2 x 10(5) donor peripheral blood T-cells/kg in 16 consecutive patients undergoing BMT from HLA-identical family members. Post-transplant immunosuppression was with cyclosporin A in conventional dosage. Eight cases developed grade I or II GvHD, limited to the skin in all cases. Only the two grade II cases required steroid therapy; the remainder were easily controlled with simple emollients. No cases of more advanced GvHD were seen. All patients engrafted promptly. With a median follow-up for the survivors of 976 days, seven cases have relapsed, with an overall projected actuarial disease-free survival of 37.5 per cent at 36 months. The overall outcome (good control of GvHD but high relapse rate) is therefore similar to that expected in patients receiving fully T-depleted marrow without post-transplant immunosuppression.

Adult↗
PubMed1992

A fully automated method for mononuclear bone marrow cell concentration.

We describe our experience in processing 40 bone marrow aspirates harvested for autotransplantation from patients with several hematological diseases using the CS-3000 blood cell separator. The bone marrow of the first 30 patients was processed by a semiautomated method, and a fully automated procedure was used for the remaining 10 cases. Both procedures were developed in our laboratory and yielded a similar average mononuclear cell recovery of 87.78% and 86.98%, respectively, and similar nucleated cell recovery (27.39% and 27.11%). The cloning efficiency of hematopoietic progenitor cells, measured as the total CFU-GM colony recovery in the in vitro cultures, did not differ between processed and recovered mononuclear cells. On the other hand, all the patients with transplants showed complete hematologic recovery, and the time to engraftment was similar to that described for other procedures. The automated procedure resulted in an average red cell removal of 97.81%, similar to the semiautomated procedure (94.19%), though with a narrower range (96.31-98.6% vs. 80.34-98.34%). The time taken to process a similar amount of bone marrow cell suspension was very different for each method: 1 hour for the fully automated vs. 2 1/2 hours for the semiautomated method to process 1,000 ml. Furthermore, the semiautomated procedure required the addition of homologous or irradiated plasma in a laminar air flow chamber, while the automated method is performed in a closed sterile system. We conclude that our procedure using the CS-3000 processor is an efficient method for fully automated large-scale processing of human bone marrow cells.

Adolescent↗
PubMed1994

High-dose consolidation with local radiation and bone marrow rescue in patients with advanced neuroblastoma.

Twenty-six children with advanced neuroblastoma were consolidated with cisplatin, BCNU, etoposide, melphalan, 21 Gy of local radiotherapy, and bone marrow rescue in a multicenter study. All patients were over 1 year of age at diagnosis. Twenty-two patients were treated in first complete or partial remission and four in second complete or partial remission. Hematologic rescue was autologous (n = 23), allogeneic (n = 2), or syngeneic (n = 1). Extrahematological toxicity involved primarily the gastrointestinal mucosa. Among five fatal toxicities, three included intestinal hemorrhage. Fourteen patients relapsed after BMT, four of them at the primary site. Seven children survive progression-free after 16-56 months. These results are essentially not different from a single-center study with the same protocol or from other published studies. The value of megatherapy for patients with advanced neuroblastoma or for a subgroup of them can only be established on a larger number of patients than most national trials accrue.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Bone marrow transplantation in Fanconi's anemia.

Fanconi's anemia (FA), a disease characterized by malformations and progressive pancytopenia, can be successfully cured by allogeneic bone marrow transplantation. Due to the sensitivity of FA cells to alkylating agents, a modified conditioning regimen including low-dose cyclophosphamide (20 mg/kg) and 5 Gy thoracoabdominal irradiation has been used. We report here our experience with bone marrow transplantation in a series of 49 patients. In HLA-identical sibling transplants, the long-term survival was 75%. Results with matched unrelated transplants are limited by the small number of patients.

Actuarial Analysis↗
PubMed1992

Treatment of recurrent metastatic medulloblastoma with intensive chemotherapy and allogeneic bone marrow transplantation.

We report here the first known case of a patient with recurrent metastatic medulloblastoma to achieve long-term disease-free survival following treatment with allogeneic bone marrow transplantation. A 27 year old white male with recurrent metastatic medulloblastoma involving lymph nodes, bone and bone marrow was treated with multi-agent chemotherapy followed by allogeneic bone marrow transplantation from an HLA-identical sibling donor. Morbidity was acceptable with moderate to severe mucositis in the immediate post transplant period and clinical grade I graft versus host disease of the skin controlled with modest doses of corticosteroids. The patient continues in unmaintained complete remission in excess of 28 months with a performance status of 100%. Allogeneic marrow transplantation following cytoreductive salvage chemotherapy is an aggressive strategy that may offer an improved likelihood of disease eradication and ultimate cure for poor prognosis patients with recurrent metastatic medulloblastoma.

Adult↗
PubMed1992

Biological aspects and clinical results of autologous bone marrow transplantation for acute myeloid leukemia.

Autologous bone marrow transplantation is a therapeutic approach that permits the administration of high-dose chemo-radiotherapy followed by the infusion of the patient's own marrow, previously collected during remission and cryopreserved. In recent years, autologous bone marrow transplantation has been increasingly used as a treatment for acute leukemias. The mechanisms underlying leukemic relapse represent the most exciting and controversial aspects of autologous bone marrow transplantation. At least three factors may be responsible for leukemic relapse in patients receiving autologous bone marrow transplantation: (1) minimal residual disease; (2) leukemic cells reinfused with the graft; (3) the lack of a graft-versus-leukemia effect. In this paper, the techniques for pharmacological marrow decontamination and the clinical results obtained with autologous bone marrow transplantation will be reviewed.

Acute Disease↗
PubMed1991

Eradication of leukaemic marrow and prevention of leukaemia relapse with total body irradiation and bone marrow transplantation.

A series of studies was carried out to determine the effect of allogeneic bone marrow transplantation (BMT) on leukaemia. The study aimed at two different, but strictly linked issues: (1) identification of the eradication capability of BMT, and (2) evaluation of the effect of BMT, both in preventing relapse and in producing long-term disease-free survival. Fifty-four patients allografted for leukaemia were evaluated at various intervals, after bone marrow transplantation, for the presence of host haemopoiesis using red-blood-cell and cytogenetic markers. Among 40 patients in remission, 10 showed functional host and donor haemopoiesis (mixed chimerism), while in 30, host haemopoiesis was never detected (complete chimerism). Seven of the 14 evaluable patients who relapsed showed the reappearance of host haemopoiesis at the time of relapse. The records of received doses of TBI indicate that patients who achieved mixed chimerism, either relapsing or not, received significantly lower doses than complete chimeras. However, some patients with complete chimerism received a TBI dose equivalent to the dose received by those with mixed chimerism, suggesting that the TBI dose is not the only factor determining the reappearance of host haemopoiesis. The data on chimerism and relapse suggest that there is heterogeneity in radiosensitivity between normal marrow cells and leukaemic cells, and further, within the different types of leukaemia. The incidence/severity of acute and chronic graft-vs-host disease (GvHD) was significantly higher in complete chimeras than in mixed chimeras suggesting that mixed chimerism may play a role in the development of tolerance; however, it could be the tolerance (i.e. absence of GvHD) which is responsible for the persistence of host haemopoietic cells. One-hundred-and-sixty-eight patients undergoing allogeneic bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) and chronic myeloid leukaemia were analyzed for risk factor associated with relapse. All patients received marrow from an HLA identical sibling after preparation with cyclophosphamide 120 mg/kg and total body irradiation (TBI) of 330 cGy on days -3, -2, -1. There was a difference of +/- 18% between the nominal total dose of 990 cGy and the actual received dose as indicated by dosimetric recordings. While interstitial pneumonitis had minimal impact on survival there was a considerable difference in the incidence of relapses. The incidence of relapse was higher in patients receiving less, than in patients receiving more than 1000 cGy respectively and this had a major impact on survival. However, transplant-related mortality was slightly higher in the group of patients receiving higher doses of TBI.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Marrow Purging↗