K. G. Blume

Long-term follow-up of 23 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with allogeneic bone marrow transplant in first complete remission

Between 1984 and 1997, 23 consecutive patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in first complete remission were treated with allogeneic bone marrow transplants from HLA-matched siblings. All patients but one were conditioned with fractionated total body irradiation (1320u2009cGy) and high-dose etoposide (60u2009mg/kg). One patient received high-dose cyclophosphamide instead of etoposide, and another patient received both drugs. Nine patients died following BMT, two from relapsed leukemia, and seven from transplant-related causes. The 3-year probabilities of disease-free survival and relapse are 65% and 12%, respectively. For patients transplanted after 1992, these probabilities are 81% (48–95%, 95% confidence interval) and 11% (2–50%), respectively. The relatively low relapse rate in this group of patients compared to published reports may reflect the enhanced anti-leukemic activity of etoposide in combination with FTBI compared to other conditioning regimens. The enhancement in overall survival for patients transplanted after 1992 may reflect improvements in supportive care, in particular, the prophylaxis of serious fungal and viral infections.

Pharmacokinetics of high‐dose etoposide

The pharmacokinetics of etoposide at doses of 1 gm/m2 to 3 gm/m2 were studied in patients with hematologic malignancies. The noncompartmental systemic clearance, mean residence time, steady‐state volume of distribution, and elimination half‐life were independent of the dose of etoposide, whereas the AUC was proportional to the dose. Comparison of these results with those reported previously indicates that etoposide exhibits linear pharmacokinetics over a thirtyfold range in doses (0.1 to 3 gm/m2).

Bone Marrow Transplantation for Acute Leukemia

Between May 1976 and December 1983, 200 patients underwent bone marrow transplantation (BMT) for hematologic malignancies at our center; 164 had acute leukemia. After administration of high dose radiochemotherapy for marrow ablation and immunosuppression, these 164 patients received marrow grafts from histocompatible sibling donors. Graft-versus-host disease prophylaxis (and therapy) consisted of either methotrexate and prednisone or cyclosporin A and prednisone. All patients have been followed for a minimum of 3 months after BMT. Results are summarized in Table 1 and Fig. 1.

High dose busulfan/etoposide as a preparatory regimen for second bone marrow transplants in hematologic malignancies

SummaryFive patients with hematologic malignancies who had relapsed between seven months and eight years after their primary bone marrow transplants were prepared with high dose busulfan/etoposide for second marrow transplanatations from the same donors who had provided the marrow for the primary transplants. The preparatory regimen was well tolerated. All patients engrafted and entered complete remission. Two patients are alive and in continued remission two and ten months after second transplant. One patient died with acute respiratory failure after two months and two patients relapsed again eight and 17 months after second marrow transplantation. The combination busulfan/etoposide may prove to be a suitable preparatory regimen for second bone marrow transplant attempts in selected patients.

Idiopathic Thrombocytopenic Purpura following Bone Marrow Transplantation

A 25-year-old female developed idiopathic thrombocytopenic purpura 1 year after undergoing bone marrow transplantation for acute myelogenous leukemia. She had a complete response after splenectomy. Th

A Silent Hemoglobin Variant Detected by Hplc: Hemoglobin City of Hope β69 (E13) Gly → Ser

A silent hemoglobin variant with substitution of serine for glycine at position 69 of the beta-chain was discovered in a healthy individual. Reverse-phase HPLC was used for globin chain separation and to separate the tryptic peptides of the variant. This variant was undetectable by conventional methods of protein separation such as electrophoresis, isoelectric focusing, and ion-exchange chromatography. This observation demonstrates the potential of reverse-phase HPLC as a tool for the search and detection of neutral substitutions in variants of hemoglobin and other proteins, and its usefulness for screening genetic variations in human populations.

Total body irradiation with a 10 mv linear accelerator in conjunction with bone marrow transplantation

Abstract Total body irradiation (1000 rad, single dose) in conjunction with chemotherapy and bone marrow transplantation is a therapy for acute leukemia. We show that a 10 MV linear accelerator is a suitable source of radiation for these procedures. Dosimetric and clinical results are presented for 25 patients who were treated between l576 and 1278.

Purification and kinetic properties of galactokinase from human placenta

Abstract Galactokinase from human placenta was purified about 350-fold using DEAE-Sephadex-A-50 chromatography followed by Sephadex-G-200 and CM-Sephadex-C-50 filtration. The final steps of purification involved electrofocusing and ammonium sulfate precipitation. In analytical disc electrophoresis the purified enzyme moved as a single protein band. Crude enzyme is extremely unstable. Purification of the enzyme increases the stability slightly. The activation energy of the enzyme was found to be 9500 Cal. Galactokinase has an absolute requirement for a divalent ion. The enzyme is maximally active in the presence of Mg 2+ , 5 m m . However, Mg 2+ could be partially replaced by Ca 2+ , Co 2+ , and Mn 2+ . The enzyme is almost completely inhibited by p -chloromercuribenzoate and partially inhibited by N -ethylmaleimide. The K m of placental galactokinase for galactose and ATP is 250 μ m and 100 μ m , respectively. Galactose-1- P appears to inhibit the enzyme in a competitive fashion with ATP with a K i of 2.0 m m . The isoelectric point of galactokinase is 5.7 and the molecular weight is 58,000. The kinetic properties of placental galactokinase have been compared to the red cell galactokinase. The K m of the placental enzyme for galactose is about twice as high as that of the red cell enzyme whereas the affinity of the placental enzyme for ATP is twice as high as that of the red cell enzyme. Co-chromatography of placental and adult erythrocyte extract resulted in the separation of two peaks of galactokinase activity, one peak with the kinetic characteristics of the purified placental enzyme and the other peak with the kinetic characteristics of the red cell enzyme.

Allogeneic bone marrow transplantation for high risk non-hodgkin's lymphoma during first complete remission

SummaryAllogeneic bone marrow transplantation from histocompatible sibling donors was performed in six patients with extranodal involvement of high grade lymphoma during first complete remission. Five patients had lymphoblastic lymphoma and one had diffuse undifferentiated lymphoma. The cytoreductive/immunosuppressive regimen consisted of total body irradiation and high dose cyclophosphamide. Four patients are alive in complete remission at 8 months, 14 months, 21 months and 47 months post transplantation. One patient who relapsed 7 months after his initial transplantation underwent a second transplantation but another relapse 17 months later led to his death. One patient died of chronic graft-versus-host disease and at autopsy there was no evidence of lymphoma. These data demonstrate that allogeneic bone marrow transplantation can produce durable remissions in patients with high grade lymphoma who present with bone marrow, central nervous system and/or skin involvement.

Fractionated total body irradiation and high dose cyclophosphamide: a preparative regimen for bone marrow transplantation for patients with hematologic malignancies in first complete remission

SummaryWe treated 73 patients with hematologic malignancies in first complete remission (acute lymphoblastic leukemia = 23 patients; acute nonlymphoblastic leukemia = 25 patients; chronic myelogenous leukemia in first chronic phase = 20 patients, and high grade lymphoma = five patients) with a uniform preparative regimen consisting of fractionated total body irradiation (1 320 cGy) and high dose cyclophosphamide (100 mg/kg), followed by allogeneic bone marrow transplantation. By radiation dosimetry we demonstrated that the calculated doses were delivered accurately and reproducibly. Actuarial survival rates (± SEM) in complete remission were as follows: Acute lymphoblastic leukemia = 74±9%; acute nonlymphoblastic leukemia = 50±11%; and chronic myelogenous leukemia = 55±11%. Actuarial relapse rates for these three diagnoses were 19±9%, 17±11%, and 0% respectively. Three of the five lymphoma patients are alive in complete remission at 22+, 28+, and 54+ months. Overall probability of survival for the 73 patients was 59±7%. Interstitial pneumonia, usually associated with cytomegalovirus infection and graft-versus-host disease, and relapse of the underlying malignancy were the major causes of death.