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PubMed1995

[Myeloablative chemotherapy with autologous bone marrow and/or peripheral blood stem cell transplantation in children with high-risk solid tumor].

Autologous bone marrow transplantation (ABMT) and peripheral blood stem cell transplantation (PBSCT) are increasingly used to support high-dose chemotherapy for solid tumors of childhood. In this review we described practical aspects of myeloablative chemotherapy rescued by ABMT, PBSCT or combination of ABMT and PBSCT for the treatment of children with high-risk solid tumor, involving our experiences in 15 cases. Indication, method of harvesting bone marrow and peripheral blood stem cells, cryopreservation, transplantation, selection of anti-neoplastic agents for preconditioning, nutritional and G-CSF support, engraftment and outcomes for prognosis were discussed. In comparing the engraftment of stem cells between ABMT and PBSCT, the acceleration of platelet and erythrocyte recovery is less impressive, although there is a tendency to more rapid recovery of granulocyte in PBSCT group. The outcomes are distinctly improved only in patients who showed complete remission after induction chemotherapy, radiation and surgical excision. A better prognosis will be conferred especially in neuroblastoma and entities of small round cell tumor. It is noteworthy that relapses can occur as distant metastasis considerable years after complete clinical remission. This may be largely contributed by contaminated malignant cells in both harvested bone marrow and peripheral blood stem cells. There is no significant difference between the relapse rates after ABMT and PBSCT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Bone marrow transplantation with major ABO incompatibility. Experience of the Bone Marrow Transplantation Unit--Francisco Gentil Portuguese Institute of Oncology, Lisbon Centre.

Thirteen patients submitted to bone marrow transplantation (BMT), HLA A and B identical, with mixed negative lymphocyte culture and major ABO incompatibility were retrospectively evaluated. Gravity sedimentation by hydroxyethyl starch was used in almost all cases to deplete erythrocytes from bone marrow (12/13): a removal rate of 90%--corresponding to an erythrocyte residual volume of 27,4 rate ml--and a nucleated cell recovery of 76% (mean values) were obtained. All patients underwent a hyperhydration regimen and received corticosteroid prophylaxis before bone marrow infusion. Considering the most important immunohematological problems associated to this type of transplant, we verified that seven patients developed minor complications and among them only one had long term consequences. In comparison with the control group, ABO identical and with minor incompatibility, the study group had delayed onset of erythropoiesis and needed greater erythrocyte transfusion support. We concluded that major ABO incompatibility does not constitute a drawback to BMT success in most patients.

ABO Blood-Group System↗
PubMed1995

Pharmacokinetics, dosimetry and toxicity of holmium-166-DOTMP for bone marrow ablation in multiple myeloma.

UNLABELLED: In this Phase I clinical trial, six multiple myeloma patients who had not responded to conventional therapy and were scheduled for bone marrow transplantation received a bone-seeking radiopharmaceutical for bone marrow ablation. The pharmacokinetics, dosimetry, and toxicity of this radiopharmaceutical were studied. METHODS: Patients received from 519 mCi to 2.1 Ci (19.2 GBq to 77.7 GBq) of holmium-166 (166Ho) complexed with a bone-seeking agent, DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic acid). The reproducibility of pharmacokinetics from multiple injections of 166Ho-DOTMP administered to these myeloma patients was demonstrated from blood (r2 = 0.926) and whole-body retention (r2 = 0.983), which allowed therapeutic parameters to be determined from a diagnostic study. RESULTS: Over 50% of the 166Ho-DOTMP injected dose was excreted within 2-3 hr postinjection, increasing to 75%-85% over a 24-hr period. Rapid blood clearance minimized radiation dose to nontarget tissue: less than 10% of the injected activity was retained in the blood pool at 1 hr postinjection, and less than 2% remained after 5 hr. The total radiation absorbed dose delivered to the bone marrow for the six patients ranged from 7.9 Gy to 41.4 Gy. CONCLUSION: All patients demonstrated severe bone marrow toxicity with a white blood cell (WBC) count < 1,000 cells/microliters, two patients exhibited marrow ablation (WBC count < 100 cells/microliters), and no other toxicity > or = grade 2 was observed in any of the patients.

Bone Marrow↗
PubMed1995

Studies on the hyperthermic sensitivity of the murine hematopoietic stem cell compartment. II. Heat effect on donor stem cells with long-term repopulating ability.

Variations in hyperthermic sensitivity among different hematopoietic progenitor and stem cell populations of the bone marrow have been previously described for clonogenic subsets responsible for short-term hematopoiesis. However, less is known of the heat sensitivity of more primitive stem cells capable of long-term repopulation in irradiated recipients. In the present study, control and heat-treated (60 minutes at 43 degrees C) donor bone marrow cells from congenic B6-Gpi-1a mice were transplanted at different cell doses (10(4), 10(5), 10(6), and 10(7) nucleated cells) in pre-irradiated (6 Gy) B6-Gpi-1b mice. The development and levels of donor marrow engraftment were determined from blood Gpi phenotyping, and the bone marrow dose required for equivalent long-term engraftment at 20 weeks provided an estimate of the surviving fraction corresponding to primitive stem cells of long-term repopulating ability (LTRA). Comparison with previous bone marrow cell survival values demonstrates that LTRA cells are less sensitive to hyperthermic treatment than other hematopoietic subsets, confirming a relationship between the heat sensitivity and the hierarchical structure of the hematopoietic stem cell compartment.

Animals↗