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Biomedical subjects

H Kaizer

Publications and source records attributed to H Kaizer.

At least 73 records · Page 4Linked to original sources

Successful engraftment of blood derived normal hemopoietic stem cells in chronic myelogenous leukemia.

The ability of blood-derived stem cells to restore hemopoietic function was investigated in a patient with chronic myelogenous leukemia with bone marrow cells containing the Philadelphia chromosome marker (Ph1+). After treatment with high dose cyclophosphamide, 26.3 X 10(9) blood mononuclear leukocytes, among them 26.2 X 10(5) granulocyte/macrophage progenitor cells (CFUC), were harvested by means of 5 successive leukaphereses when the bone marrow cells had converted to Ph1--. When the patient entered the aggressive phase (blast crisis), myeloablative treatment with busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) was given, followed by transfusion of the cryopreserved blood leukocytes. Restoration of marrow and blood cellularity was completed about 20 days after this autologous blood stem cell transplantation (ABSCT). Marrow CTUC recovery was complete 2 weeks after ABSCT, and all karyotypes of the patient's marrow cells were free of the marker chromosome. The patient died of toxicity but with normal bone marrow cellularity. This report confirms the therapeutic usefulness of autologous blood-derived stem cells harvested in remission in restoring hemopoietic function after myeloablative treatment.

Adult↗

Ovarian involvement in neuroblastoma.

A case of neuroblastoma involving the ovaries bilaterally at diagnosis is reported. A review of previous cases of neuroblastoma at Johns Hopkins Hospital revealed no previous occurrence of ovarian metastatic disease at diagnosis, but involvement in about one-third of cases at autopsy. This appears to be a more common site of metastatic disease than has been previously recognized. The significance of this site of metastases in neuroblastoma is unknown.

Adrenal Gland Neoplasms↗

Cryopreserved autologous bone marrow transplantation in the treatment of selected pediatric malignancies: a preliminary report.

We have shown that it is possible to collect and viably store sufficient numbers of stem cells to hematologically reconstitute patients following marrow-lethal doses of chemoradiotherapy. While no current procedure can be guaranteed to eliminate clonogenic tumor from the bone marrow, the fact that hematopoietic stem cells capable of reconstituting the host can be obtained after intensive chemotherapy makes it possible to clear microscopic foci of tumor from the marrow prior to storage. Such patients are now included in our protocol. The initial treatment results indicate that, in selected circumstances, tumor in otherwise refractory patients can be eliminated or partially controlled by a single intensive pulse of chemoradiotherapy with severe but acceptable extramedullary toxicity. The fact that patients can be rescued from otherwise lethal myelotoxicity by the reinfusion of cryopreserved autologous bone marrow permits wider exploration of new, more intensive cytoreductive regimens in a variety of cancers.

Bone Marrow Transplantation↗

Autologous bone marrow transplantation in the treatment of selected human malignancies: The Johns Hopkins Oncology Center Program.

Preliminary clinical trials using cryopreserved autologous bone marrow reinfusion have now been carried out at our institution in 5 children and 2 adults with advanced stages of neuroblastoma, rhabdomyosarcoma, non-Hodgkin's lymphoma and small cell carcinoma of the lung. Normal numbers of in vitro colony forming cells (CFU-C) were obtained from these patients despite prior courses of combination chemotherapy. The dose of marrow cells cryopreserved ranged from 1-6 X 10(8) cells/kg and recovery of CFU-C after thawing averaged 50%. Partial or complete hematologic reconstitution was achieved in all patients. The time for recovery ranged from 10-43 days for leukocytes (greater than 1000 cells/mm3) and 23-45 days for platelets (greater than 50,000/mm3). Two patients have died of interstitial pneumonitis due to cytomegalovirus. Three patients have died of recurrent tumor at 40, 48 and 156 days post-transplant. Two patients have had significant therapeutic benefit. One of these had a stable partial response permitting the use of further post-transplant therapy and is alive and well 16+ months post-transplant. The other patient had a complete response and remains tumor-free 25+ months following therapy. We conclude: 1) Autologous bone marrow reinfusion permits hematologic reconstitution following marrow-ablative therapy. 2) A quantity of marrow sufficient for this purpose remains viable following cryopreservation even when obtained from patients previously exposed to chemotherapy. 3) Autologous bone marrow reinfusion now allows the exploration of more intensive cytoreductive therapy in selected malignancies.

Antineoplastic Agents↗

A simplified assay for methotrexate in biological fluids using a crude yeast lysate.

Routine pharmacokinetic monitoring of methotrexate levels in biological fluids appears to be important for clinical applications involving large doses of methotrexate with leucovorin rescue. Recently several laboratories have independently described a competitive radiobinding assay that has the necessary sensitivity, precision and simplicity for this purpose. This study describes a modification of this assay method using a lysate of dry, active yeast as a source of binding activity. The assay is sensitive at blood concentrations of about 1 nM. No significant interference can be shown with naturally occurring folates. Specificity has also been shown by recovery experiments from serum and urine. Thus this modified assay matches the previously described radiobinding assays but with the advantage of using a methotrexate binding reagent that is readily available and quite inexpensive.

Humans↗

Prognostic factors in neuroblastic tumors.

Data of 101 patients with neuroblastic tumors from 1950 to1974 at The Johns Hopkins Hospital have been abstracted onto specially designed summary sheets, and subjected to multifactorial analysis. One-third of the 21 benign ganglioneuromas showed evidence for spontaneous maturation. The overall cure rate among the malignant tumors was 39%. Cures were higher with an extraabdominal primary, with more mature histologic differentiation, and if excision, even partial, was carried out. Neither radiotherapy nor evolving modalities of chemotherapy appear to have had benefit over this 25-yr period. An age at diagnosis less than 2 yr, and a less extensive clinical stage both were independent predictors of survival. The apparent effects of a favorable site of tumor origin, or more mature histologic differentiation were not of major impact in and of themselves, but correlated better with clinical stage. Two prognostic schemata, based on stage plus age, and stage plus histologic differentiation plus age respectively, proved to be 95% accurate in our experience. With more extensive evaluation and experience, either or both may be helpful in the management of malignant neuroblastic tumors, and assessment of therapeutic regimens.

Adolescent↗

Immunologic and morphologic studies of T cell lymphoma.

Thymic-independent (B) lymphocytes, thymic-independent (T) lymphocytes and histiocytes may be distinguished by the presence of certain surface markers. In addition B and T lymphocytes have been reported to show distinctive surface architecture by scanning electron microscopy. Neoplastic cells from a lymph node and cerebrospinal fluid of a patient with a diffuse malignant lymphoma of the poorly differentiated lymphocytic type were examined in frozen sections and cell suspensions for the presence of surface immunoglobulin and the antigen-antibody-complement (IgMEAC) receptor of B lymphocytes, the presence of the cytophilic antibody (IgGEA) receptor of histiocytes and the ability to form nonimmune rosettes with sheep red blood cells (E) characteristic of T lymphocytes. Cells from the lymph node were also studied by scanning electron microscopy. The majority of neoplastic cells from the lymph node and cerebrospinal fluid formed rosettes with E, but lacked surface immunoglobulin and failed to bind IgMEAC or IgGEA. By scanning electron microscopy the neoplastic cells, although larger in diameter, showed surface architecture similar to normal lymphocytes with a varying number of surface microvilli. These studies suggest that the malignant cells of this lymphoma are of thymic type.

Adolescent↗