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Biomedical subjects

A Montuoro

Publications and source records attributed to A Montuoro.

At least 19 recordsLinked to original sources

Allogeneic marrow grafts from donors with congenital chromosomal abnormalities in marrow cells.

To determine whether siblings with chromosomal abnormalities in marrow cells which are associated with cellular defects (e.g. Down syndrome or heterozygosity for Fanconi syndrome) are suitable donors for allogeneic bone marrow transplants, we have reviewed the patient files at the Fred Hutchinson Cancer Research Center (FHCRC) and carried out a survey among member centres of the International Bone Marrow Transplant Registry (IBMTR). The 57 of 253 (23%) member centres which responded to the survey reported seven transplants from donors with the following conditions: Down syndrome (n = 2), suspected heterozygotes for Fanconi syndrome (n = 3), and 47,XXX syndrome (n = 2), among a total of 5,561 allogeneic transplants from HLA-identical siblings. Adding the three cases seen at the Fed Hutchinson Cancer Research Center among 2,927 HLA-identical sibling transplants during 1992 resulted in 10 transplants among 8,488 cases transplanted overall: four with Down syndrome, four suspected of being heterozygous for Fanconi syndrome, and two trisomy X. Three out of four grafts from siblings with Down syndrome had complications, including poor graft function (n = 2) and graft failure (n = 1). Two of four recipients of marrow from presumed Fanconi syndrome heterozygotes presented with poor graft function and a third recipient developed graft failure after initial evidence of engraftment. The two patients given marrow from siblings with 47,XXX syndrome engrafted uneventfully. The experience reported here shows a low frequency of encountering an HLA-identical sibling donor who has chromosomal abnormalities in marrow cells consistent with Down syndrome or heterozygosity for Fanconi syndrome, about one case among 1,000 transplants. The much higher than expected incidence of graft problems with marrow from such a donor would make it reasonable to look either for an alternative marrow donor or consider an autologous transplant, in case a sibling marrow donor with Down syndrome or heterozygosity for Fanconi syndrome is encountered, although a donor with trisomy X seems acceptable.

Adolescent

Progenitor cells purging: negative selection.

Disease relapse after autologous bone marrow transplantation (ABMT) may arise from residual tumor in the recipient and/or from cancer cells that are reinfused. The aim of purging by negative selection is to remove tumor cells from the marrow without adversely affecting the engraftment potential of the normal cell. We report the results of a study on fifty-six patients (pts) with non Hodgkin's lymphoma or acute leukemia submitted to ABMT after immunomagnetobead (IMB) purging (11 pts), Maphosphamide purging (31 pts) and no purging (14 pts). The IBM procedure involved one incubation of 3 monoclonal antibodies (CD10, CD19 and CD22) and two incubations with magnetic beads (Dynabeads M-450). The median recovery of mononuclear cells and CFU-GM was 40% and 45% after IMB purging and 84% and 5% after Maphosphamide purging respectively. The rate of leukocyte, neutrophils and platelets recovery following ABMT was similar in the three groups of pts, although platelet recovery was slow in patients received graft purged with Maphosphamide. Our study confirms the clinical feasibility of the IMB procedure, but only randomized studies will be able to definitely address the question of the clinical utility of purging.

Adolescent

Therapy of 'high risk' myelodysplastic syndromes with an association of low-dose Ara-C, retinoic acid and 1,25-dihydroxyvitamin D3.

Forty-four patients with high risk primary myelodysplastic syndromes and an excess of marrow blasts were treated with a combination of low-dose Ara-C, retinoic acid and vitamin D3. Morphological subtypes were refractory anemia with excess of blasts (RAEB) in 16, RAEB in transformation (RAEB-T) in 20 and chronic myelomonocytic leukemia (CMML) in eight patients. The therapy was continued in responders until relapse or death. The results were compared to those of a matched control of 44 patients given a supportive therapy only. In the treated group the overall response rate was 50% (75% in RAEB, 50% in RAEB-T and 0% in CMML) and the survival was significantly better than in the control group (P < 0.025). Comparing separately each FAB subgroup gave statistical evidence that the treatment prolonged the survival in the RAEB-T subgroup only (P < 0.002). The median duration of response was 15 months and the survival in responders was statistically better than in non-responders (P < 0.0001). Myelosuppression has been the most important side effect, however, no death related to the treatment was observed. Our study suggests that patients with RAEB-T, who are not suitable candidates for aggressive chemotherapy, could benefit from our treatment schedule. The long duration of therapy seems to be of value for patients achieving a response in order to prolong the survival. The toxicity is acceptable and the therapy can be given on an outpatient basis.

Aged

A technique for isolation of bone marrow cells using hydroxyethyl starch (HES) sedimentation agent.

Various methods have been investigated to concentrate hemopoietic stem cells before in vitro treatment and cryopreservation. Each procedure requires various degrees of cell manipulation; moreover, the extent of purification of the stem cell fraction depends on the further use of bone marrow. Fifty four bone marrows were treated with hydroxyethyl starch (HES) to isolate the mononuclear cell population. The manipulation with HES permitted to concentrate marrow stem cells in a small volume with removal of unwanted granulocytes, red blood cells and the donor isohemagglutinins in the major ABH incompatibility. We describe here a manual method which permits the transfusion of a very few number of red cells without depletion of progenitor cells and thus delay of engraftment.

Blood Group Incompatibility

Immunomagnetic purging procedure for autologous bone marrow transplantation in lymphoid malignancies.

In this report we describe the use of the immunomagnetic depletion of tumor cells from harvested bone marrow in two patients with acute lymphoblastic leukemia. The immunomagnetic procedure of purging involved one incubation of the marrow cells with a mixture of 4 monoclonal antibodies which bind to antigens of CD10 (ALB2), CD19 (HD37), CD20 (B1) and CD22 (HD39). Two incubations with magnetic beads (Dynabeads M-450) covered with antimouse antibodies followed by magnetic separation were performed. The bead/target B cell ratio was 50:1. After purging the recovery of mononuclear cells was 56% and 40%, while the recovery of CFU-GM was 45% and 38% respectively. Both patients engrafted rapidly without serious complications. One patient relapsed 4 months after transplant, the other remains in complete remission after 5 months. Our results confirm that the use of immunomagnetic beads is a simple, safe and reproducible technique to remove tumor cells before ABMT in patients with B malignancies using a broad mixture of MoAbs. However only a randomized trial using autologous marrow purged or not will clarify the effective clinical value of the procedure.

Adolescent

Alpha-2a-interferon/melphalan/prednisone versus melphalan/prednisone in previously untreated patients with multiple myeloma.

Alpha-2a-interferon (IFN) has demonstrable activity in advance and refractory multiple myeloma (MM), because of the in vitro synergism between IFNs and cytotoxic agents we report the preliminary results of a therapeutic trial of 50 patients with MM. Twenty-eight patients were randomized to receive melphalan plus prednisone (MP) and 22 were randomized to receive IFN plus MP (IFN-MP). Criteria for response, progression and relapse were those of the Southwestern Oncology Group. 95% of the patients receiving IFN-MP responded to therapy as opposed to 68% of the patients receiving MP (P less than 0.05). Response was independent of M-component immunoglobulin class but in stage III it was higher in the IFN-MP group than in the MP group (P less than 0.05). The combination IFN-MP was well tolerated without unusual or unexpected toxic effects. The response duration time was longer in the IFN-MP group than in the MP group (P less than 0.025). The median survival was 80 weeks in the MP group and in the IFN-MP group the 93% of patients were still alive after 90 weeks (P less than 0.025). Our results show that the use of the IFN as an adjuvant to MP improves the percentage of responders, the response duration time and the median survival of untreated patients with MM.

Adult

Empiric antibiotic and antifungal therapy for granulocytopenic patients with acute leukemia.

A prospective study was undertaken to determine the effectiveness of an empiric antibiotic treatment employing the combination of a beta-lactam and an aminoglycoside followed in non responders by vancomycin and amphotericin B after 48 and 96 hours respectively. We have evaluated 180 febrile episodes in 102 granulocytopenic leukemic patients. Febrile episodes (44%) were microbiologically documented; 29% were only clinically documented and 27% were possible. In the 180 evaluable episodes treated with a beta-lactam and an aminoglycoside the overall response rate was 61%. In non responders the addition of vancomycin increased the response rate to 83% and the subsequent addition of amphotericin B moved the total responders to 96%. Antibiotic related side effects were minimal. These data suggest the importance of an empiric strategy for treatment of bacterial infections arising in granulocytopenic patients. An early empiric antifungal therapy also appears necessary to control clinically undetected fungal invasion.

Acute Disease

Y chromosome duplication: a minor route evolutive pattern in CML.

2 patients have been investigated, in which Y chromosome duplication occurred during blastic transformation of chronic myelocytic leukaemia. Comparison of cytogenetic findings and survival data in our cases and in previously reported individuals, suggests preliminary conclusions about the prognostic significance of this aneuploidy. Y chromosome gain does not seem to represent per se an unfavourable event, unless it is associated with additional chromosome change.

Aneuploidy

Cytogenetic studies in acute leukaemias. Prognostic implications of chromosome imbalances.

Consistent cytogenetic abnormalities have been detected in the bone marrow cells of 19 out of 33 patients (57.57%) with a recent diagnosis of acute leukaemia. Chromosome imbalances were apparently non-random, chromosomes 8, 17, 20 and 21 being more frequently involved. The median survival in the patients' group with abnormal metaphases was 55 vs. 210 days in patients with only normal metaphases. In the former group complete remission was obtained in 2 of 3 ALL patients and in 4 of 16 ANLL patients. Major karytypic abnormalities were consistently found in 5 subjects with EL. Peripheral blood culture lymphocytes showed a 9qh polymorphism in 2 of 35 patients and sporadic or consistent chromosome abnormalities in 6.

Chromosome Aberrations

Primary plasmacytoma of the testis. A case report.

The authors describe a case of multiple myeloma that developed several extraskeletal localizations. They evaluated the relation between the onset of the testicular tumor and the following myeloma characteristics: tumor burden, clinical phase, response to therapy and prognostic significance. The patient presented a rapid and dramatic clinical evolution of the disease with extensive spread also to the soft tissues of the abdominal wall. Chemotherapy did not achieve any effect and the patient died due to progression of the myeloma.

Aged

Blood stem cells autografts in patients with high risk multiple myeloma.

Five patients with high risk multiple myeloma not responsive to standard chemotherapy were treated by high-dose chemotherapy (Melphalan, Cyclophosphamide) (HDC) and total body irradiation (TBI) followed by autografting with blood stem cells. These cells were previously collected by leukaphereses from eight to twelve occasions during hematopoietic recovery following profound aplasia induced by each course of intensive chemotherapy (Vincristine, Adriamycin, Cyclosphosphamide, Prednisone) when the patient reached a neutrophil count of 1,000/microliters and a platelet count of 100,000/microliters. No patients had evidence of tumor plasmacells in leukaphereses products using cytology, immunocytochemistry and immunofluorescence. At this time the patient 5 is not evaluable because of the short follow-up. One died at day 30 from heart failure. All living patients achieved a complete remission which persisted at a follow-up of 300, 261 and 136 days. Autologous blood derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. Our results indicate the feasibility of this therapeutic approach over allogenic or autologous bone marrow transplantation in selected patients with high tumour mass multiple myeloma.

Adult