PubMed Health⌕ Search

Biomedical subjects

G Spitzer

Publications and source records attributed to G Spitzer.

At least 37 records · Page 2Linked to original sources
PubMed1993

Design of preparative regimens for stem cell transplantation in breast cancer.

We have evaluated tandem cycles of a tri-drug combination, termed CVP (cyclophosphamide, etoposide [VP-16], and cisplatin [Platinol]), at four levels in more than 300 patients with various types of tumors. Tandem CVP appears to be at least therapeutically equivalent to alternatives. A second potentially non-cross-resistant combination of mitoxantrone and thiotepa (MT), with or without etoposide, has been used in sequence following CVP to improve long-term, disease-free survival in patients who have multiple metastatic sites, who relapse shortly after adjuvant therapy, or who show other unfavorable clinical features. A combination of MT and etoposide (MVT) achieved an overall response rate of 61% in 32 patients with metastatic or refractory breast cancer. The etoposide was then eliminated to decrease the major toxicities of this regimen. MT was subsequently given to 37 evaluable patients prior to bone marrow infusion. The overall response rate was 48.5% Thirty patients with metastatic breast cancer were then treated with induction therapy, a cycle of CVP, and then a cycle of MT. Given the low complete remission (CR) rate to induction therapy in these patients, the CR rate achieved with CVP-MT was encouraging. Further studies are ongoing.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Tandem transplants in solid tumors: marrow versus peripheral stem cell transplant: peripheral blood cells as now practiced are not the whole answer.

We have performed sequential studies examining the modification of hematopoietic toxicity after the administration of high-dose cyclophosphamide, etoposide, and cisplatin (CVP). The sequential studies include a comparison of the influence of autologous bone marrow transplantation (ABMT) on hematopoietic recovery after CVP, with or without growth factors. These studies demonstrate a significant shortening of the duration of neutropenia with ABMT, but minimal impact on the number of infectious episodes, when compared to those not receiving ABMT. The addition of mobilized peripheral blood stem cells (PBSC) to ABMT followed by growth factor was found to enhance platelet recovery, but did not significantly further reduce the period of absolute neutropenia. Subsequent studies show that similar early hematopoietic recovery can be achieved by use of peripheral blood stem cells alone, pheresed following several days of subcutaneous administration of recombinant growth factors, but neutrophil recovery is more rapid with use of growth factor after PBSC infusion. Using the product of two phereses for each cycle of recovery appears to result in similar rates of hematopoietic engraftment after each cycle of CVP. In conclusion, the use of peripheral blood stem cells alone following sequential high dose CVP is associated with rapid neutrophil and platelet recovery. Caution should be exercised when using PBSC alone after high dose therapy, due to the lack of platelet recovery in some instances, which can be overcome by reinfusion of backup marrow. Thus, studies evaluating the role of PBSC after high dose therapy should continue.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

High dose chemotherapy followed by autologous hematopoietic rescue in Hodgkin's disease: long-term follow-up in 128 patients.

BACKGROUND: There is little long-term follow-up information after autologous transplantation for Hodgkin's disease. We evaluated the influence of various prognostic factors and examined the outcome in 128 such patients. PATIENTS AND METHODS: Patients received high dose cyclophosphamide, carmustine, and etoposide followed by autologous hematopoietic rescue. RESULTS: Patients have been observed between 50-130 months (median 77 months) following transplantation. Overall survival at four years is estimated as 45 percent, and failure-free survival as 25 percent. The best results were seen in patients with a good performance status, who had failed at most one prior chemotherapy regimen. Failure-free survival at four years is estimated as 53 percent for this group. Relapses more than 24 months after transplantation were seen in 11 patients. Five patients developed myelodysplastic syndromes. Three patients became pregnant after the transplant. CONCLUSIONS: Prolonged failure-free survival may be observed following high dose chemotherapy and autologous hematopoietic rescue in patients with Hodgkin's disease. Superior results were seen in patients without extensive prior chemotherapy and in those with a good performance status. Late relapses and deaths from secondary myelodysplastic syndromes mandate prolonged follow-up after autologous transplantation for Hodgkin's disease.

Adolescent↗
PubMed1993

Cisplatin-CBV with autologous bone marrow transplantation for relapsed Hodgkin's disease.

The use of high-dose cyclophosphamide, carmustine, and etoposide (CBV) with autologous bone marrow transplantation (ABMT) results in long-term disease-free survival of about 30% in patients with relapsed Hodgkin's disease. Laboratory and clinical data show that cisplatin is synergistic with etoposide and carmustine, with non-overlapping extramedullary toxicity. Twenty-one patients with relapsed Hodgkin's disease that had progressed after both MOPP-like and ABVD-like regimens were treated with CBV plus cisplatin (90 mg/m2) and ABMT. The CR rate was 55%; the three-year disease-free and overall survival were 29% and 38% respectively; these results are comparable to prior experience with CBV. Performance status was strongly correlated with achievement of CR, survival, and time to treatment failure. Nephrotoxicity was seen in 3 patients, and ototoxicity in 1 patient. Although cisplatin could be added to CBV with minimal additional toxicity, the results obtained in this small patient population were not better than those of the earlier regimen. A larger trial in patients not previously exposed to cisplatin may better define the role of its addition to CBV.

Adolescent↗
PubMed1993

Dose escalation of mitoxantrone given with thiotepa and autologous bone marrow transplantation for metastatic breast cancer.

High-dose chemotherapy given with autologous bone marrow support has resulted in significant tumor responses in the majority of patients with metastatic breast cancer, a minority of which are durable. To improve on these results, we are developing high-dose preparative regimens which may be given in successive cycles, each with autologous bone marrow transplantation (ABMT), over a short duration. In this report, 44 patients with metastatic breast cancer were treated with thiotepa (total dose: 900 mg/m2) and mitoxantrone (MT), administered in a dose-escalation fashion, with ABMT. The dose-limiting non-hematologic toxicity of mitoxantrone was cardiotoxicity, with the maximum tolerated dose being 50 mg/m2 Mucositis and pneumonia were also frequent treatment-related side-effects. The overall tumor response rate was 49% in this heavily pre-treated group of patients. We are currently evaluating the toxicity and efficacy of tandem non-cross-resistant transplant regimens, using the MT combination for the second cycle of therapy, in patients with metastatic breast cancer sensitive to standard dose chemotherapy.

Adult↗
PubMed1992

Influence of mobilized peripheral blood cells on the hematopoietic recovery by autologous marrow and recombinant human granulocyte-macrophage colony-stimulating factor after high-dose cyclophosphamide, etoposide, and cisplatin.

Peripheral blood cells (PBC) can hasten hematopoietic recovery after high-dose chemotherapy. To determine if PBC apheresed after mobilization further enhance hematopoietic recovery over that achieved with autologous bone marrow (ABM) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), 14 patients with metastatic solid tumors were supported by ABM and rhGM-CSF during the first course of high doses of cyclophosphamide, etoposide, and cisplatin (CVP) and 11 of these 14 patients by mobilized PBC with ABM and rhGM-CSF during the second CVP. Each patient served as his or her own control. Identical doses of CVP were administered in both courses: cyclophosphamide 5.25 g/m2, etoposide 1,200 mg/m2, and cisplatin 165 to 180 mg/m2. PBC were collected on day 10 after mobilization with cyclophosphamide (3 g/m2) intravenously (IV) on day 1, doxorubicin (50 mg/m2) as a continuous IV infusion over 48 hours starting day 2, and rhGM-CSF as a daily 4-hour IV infusion starting day 4 at 0.6 mg/m2 for 14 days. Comparing recovery in the 11 patients to receive two cycles of therapy, the median days to an absolute neutrophil count of 0.1 x 10(9)/L and 0.5 x 10(9)/L were not statistically significant between the two courses; neither was there a difference in the incidence of fever and bacteremia. The median number of days to platelet count of 0.02 x 10(12)/L unmaintained by platelet transfusion was 20 from marrow infusion for course 1 and 16 for course 2 (P = .059). The median number of days to a platelet count of 0.05 x 10(12)/L was significantly shortened: 24 and 19 days for courses 1 and 2, respectively (P = .045). Patients who received PBC required fewer number of platelet transfusions. Extramedullary toxicities were not different between the groups. Our finding of enhanced early recovery of platelets and reduced platelet transfusion requirement is in concordance with other studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Polyclonal hematopoiesis in interferon-induced cytogenetic remissions of chronic myelogenous leukemia.

Interferon (IFN) therapy of early chronic myelogenous leukemia (CML) frequently produces partial or complete cytogenetic remission of the disease. Patients with complete cytogenetic remission often continue on therapy for several years with bone marrow showing only diploid (normal) metaphases. We studied hematopoiesis in five female patients with major cytogenetic remissions from CML during IFN therapy. Clonality analysis using the BstXI PGK gene polymorphism showed that granulocytes were nonclonal in all patients during cytogenetic remission. BCR region studies showed rearrangement only in the one patient whose remission was incomplete at the time of sampling. Granulopoiesis is nonclonal in IFN-induced remissions of CML and may be derived from normal hematopoietic stem cells.

Clone Cells↗
PubMed1992

Second bone marrow transplants for relapsed leukemia.

Seventeen patients who had a relapse at a median of 9 months after marrow transplant (14 allogeneic and three syngeneic) received second transplants. Eight patients were in remission when transplanted. Of the nine patients with active disease at the time of transplant, six had complete remissions, and one converted from blastic to chronic phase of chronic myelogenous leukemia. The median survival was 9 months (95% confidence interval, 4 to 17 months). Four patients died within 100 days of transplantation, and three were disease-free. Ten patients died after 100 days, all except two of disease relapse. Five patients had remissions that were greater than 12 months and longer than the remission after their first transplant (inversions). Three patients remain alive and disease-free at 37+, 55+, and 61+ months, the former two despite remissions of less than 1 year after their first transplant. Second transplants with a different cytoreductive regimen can eradicate disease resistant to prior myeloablative treatment; some patients may benefit from second transplants, even if the first transplant only achieves a short remission.

Adolescent↗
PubMed1992

Allogeneic bone marrow transplantation for hematological malignancies following etoposide, cyclophosphamide, and fractionated total body irradiation.

Forty-three patients received etoposide, cyclophosphamide, and fractionated total body irradiation before allogeneic marrow transplantation. Fifteen patients had chronic myelogenous leukemia in chronic phase or acute leukemia in first remission (standard risk) and twenty-eight patients with more advanced disease (high risk). All patients received etoposide 1,500 mg/m2 intravenously on day -8, cyclophosphamide 60 mg/kg/day intravenously on days -7 and -6, and total body irradiation at 170 cGy twice a day on days -3, -2, and -1. During the first 100 days 12 high risk patients (43%) died from causes unrelated to relapse while none of the standard risk patients died. Renal and hepatic dysfunction were also significantly increased during the first 14 days in the high risk group. The addition of 1,500 mg/m2 of etoposide to the cyclophosphamide and total body irradiation was well tolerated for patients with standard risk. However, the regimen was poorly tolerated with high mortality in patients with more advanced disease.

Acute Disease↗
PubMed1992

Autologous bone marrow transplantation in solid tumors.

Recent studies in autologous bone marrow or peripheral blood transplantation in solid tumors are discussed. The toxicity and activity of high-dose cisplatin or carboplatin combined with etoposide and other drugs are described. The results of trials in nonseminomatous germ cell tumors, neuroblastoma, ovarian cancer, and brain tumors are detailed and discussed. The impressive antitumor activities noted in certain subgroups should lead to an early application of these strategies before drug resistance becomes prevalent.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Intensive combination chemotherapy and autologous bone marrow transplantation leads to the reappearance of Philadelphia chromosome-negative cells in chronic myelogenous leukemia.

Fifteen patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who were ineligible for allogeneic bone marrow transplantation (BMT) or alpha-interferon therapy were included in this study. Eight patients were in the first late chronic phase, five were in the second chronic phase, one was in the accelerated phase, and one was in the blastic phase. Autologous bone marrow cells (median, 2.5 x 10(8) nucleated cells/kg) were stored at a median of 30 months after diagnosis. Patients were treated with cyclophosphamide (1.5 g/m2 daily for 4 days), carmustine (BCNU) (300 mg/m2), and etoposide (VP-16) (250 mg/m2 daily for 3 days) (CBV), followed by reinfusion of autologous bone marrow. Hematopoietic recovery was rapid, and toxicity was mild to moderate in 14 patients. One patient died of cytomegalovirus pneumonitis. Eight of 15 patients showed Ph suppression to less than 90% Ph-positive metaphases after autologous BMT. Major cytogenetic responses (Ph suppression to less than 35% Ph-positive metaphases) developed in four patients. Cytogenetic responses were observed in 4 of 11 patients infused with 100% Ph-positive marrows, and in all 4 patients infused with Ph-mosaic marrows (mixture of diploid and Ph-positive cells). Better results were observed when autologous BMT was performed in the chronic phase compared with the advanced phases. The major cytogenetic responses have lasted for 3, 4, 12, and 15+ months, whereas minor cytogenetic responses lasted for only a short time (less than 2 months). Three of seven patients (43%) in the chronic phase with previous resistance to alpha-interferon therapy became sensitive to alpha-interferon therapy after autologous BMT. The authors concluded that intensive chemotherapy followed by autologous BMT produced cytogenetic remissions in patients with Ph-positive CML and reinduced disease sensitivity to alpha-interferon therapy in patients previously resistant to it. This is particularly useful when treatment is given during the chronic phase and stem cells are collected at a time of previous cytogenetic remission.

Adult↗
PubMed1991

Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma.

The CD34 antigen is expressed by 1% to 4% of human and baboon marrow cells, including virtually all hematopoietic progenitors detectable by in vitro assays. Previous work from our laboratory has shown that CD34+ marrow cells can engraft lethally irradiated baboons. Because the CD34 antigen has not been detected on most solid tumors, positive selection of CD34+ cells may be used to provide marrow cells capable of engraftment, but depleted of tumor cells. In seven patients with stage IV breast cancer and two patients with stage IV neuroblastoma, 2.5 to 17.5 x 10(9) marrow cells were separated by immunoadsorption with the anti-CD34 antibody 12-8 and 50 to 260 x 10(6) positively selected cells were recovered that were 64 +/- 16% (range 35% to 92%) CD34+. The patients received 1.0 to 5.2 x 10(6) CD34-enriched cells/kg after marrow ablative therapy. Six patients engrafted, achieving granulocyte counts of greater than 500/mm3 at 34 +/- 10 (range 21 to 47) days and platelets counts of greater than 20,000/mm3 at 46 +/- 14 (range 28 to 66) days posttransplant. Five of these patients showed durable engraftment until the time of death 82 to 386 days posttransplant. One patient failed to sustain engraftment associated with metastatic marrow disease. Three patients died at days 14, 14, and 17 posttransplant, two of whom had evidence of early engraftment. These studies suggest that CD34+ marrow cells are capable of reconstituting hematopoiesis in humans.

Antigens, CD↗
PubMed1991

Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation.

Fifty patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) who had relapsed after a complete remission induced by an Adriamycin-containing chemotherapy regimen participated in this prospective pilot study. The patients ranged in age from 16 to 60 years (median 42 years). All patients received dexamethasone, high-dose cytarabine, and cisplatin (DHAP) for two courses at 3- to 4-week intervals. Patients achieving a partial or complete response were scheduled to receive involved-field radiotherapy and high-dose carmustine, etoposide, cytarabine, and cyclophosphamide (BEAC), followed by autologous bone marrow transplantation (ABMT). Among 48 evaluable patients (ie, 1 was lost to follow-up and 1 had no measurable disease) 7 patients obtained a complete response (CR) and another 21 patients achieved partial response (PR), whereas the remaining 20 patients failed. One responder died of treatment-related toxicity, and six others declined ABMT. The patient with no measurable disease did not progress on DHAP and was submitted to ABMT. Twenty-two patients underwent ABMT [20 with BEAC and 2 with cyclophosphamide plus total body irradiation (TBI)] of whom 2 (9%) died of toxicity and 10 relapsed. One patient was a suicide at 28 months post-ABMT in CCR and 9 are alive disease-free 24 months to 32 months (median 30 months) post-ABMT. The actuarial 2-year event-free survival for patients undergoing transplantation is 40%. This prospective multicenter trial documents the ability of DHAP followed by ABMT to produce durable complete remission in a significant proportion of patients with relapsed aggressive NHL. Forty-four percent of all patients with relapsed lymphoma who entered the study actually underwent ABMT and 20% of the total group are projected to be long-term disease-free survivors.

Adolescent↗
PubMed1991

An effective acute graft-vs.-host disease prophylaxis with minidose methotrexate, cyclosporine, and single-dose methylprednisolone.

Cyclosporine and methotrexate at standard doses (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6, and 11, total 45 mg/m2) are effective in the prophylaxis of acute graft-vs.-host disease. However, the combination has significant early toxicities with delayed engraftment, increased mucositis, and hepatotoxicity. We modified the combination by adding single-dose methylprednisolone and lowered the total dose of methotrexate to 35 mg/m2 (5 mg/m2 on days 1, 3, and 6, and then 10 mg/m2 on days 11 and 18) and then to 20 mg/m2 (5 mg/m2 on days 1, 3, 6, and 11) in an attempt to decrease these side effects in two sequential consecutive groups of patients. We demonstrated that the modified regimens maintained the efficacy with reduced toxicities. The rate of engraftment was comparable to cyclosporine alone and the hepatotoxicity was reduced with reduced doses of methotrexate. Factors such as early immunosuppression of the host, intravenous immunoglobulin, the timing of steroid administration, nucleotide free diet and germ free environment may contribute to the effectiveness of the combination and permit reduction of methotrexate dose.

Bone Marrow Transplantation↗
PubMed1991

Detection of micrometastatic tumor cells in bone marrow of breast carcinoma patients.

To determine the incidence and clinical significance of micrometastases in the bone marrow of breast carcinoma patients, we performed an immunoalkaline phosphatase assay using anticytokeratin (AE1, AE3, MAK-6) and antiepithelial (113F1, 260F9, 317G5) antibodies on the bone marrow aspirates of 71 stage IV disease patients with either recurrent regional or distant metastases. Although we detected tumor cells within the bone marrow of 38% of these patients with this assay, no significant correlation was seen with patient's age, menopausal status, bone scan, bone marrow core histology, response to induction chemotherapy, number of metastatic sites, dominant site of metastasis, or subsequent clinical outcome. The clinical parameters that were associated with improved survival were one dominant site of metastatic disease and regional soft tissue recurrence without distant disease.

Adolescent↗
PubMed1991

Autotransplantation in solid tumors.

Studies are described of high-dose therapy in metastatic breast cancer, early stage breast cancer, stage IV neuroblastoma, recurrent or bulky disease testicular cancer and Ewing's sarcoma. The outcome in these subgroups with conventional therapy is described for comparison. The results of these studies suggest that high-dose therapy with autologous marrow support increases the proportion of patients with long-term survival without evidence of disease. Newer supportive care and recurrent high-dose therapy cycles of non-cross resistant regimens may improve outcome further in these diseases and increase the application to more resistant tumors.

Adult↗
PubMed1991

Autologous bone marrow transplantation in solid tumors.

The design and results of recent studies of high-dose therapy in metastatic breast cancer, early-stage breast cancer, stage IV neuroblastoma, recurrent or bulky disease and testicular cancer, particularly the proportion of long-term disease-free survivors, are described. The outcome in these subgroups with conventional therapy is described for comparison. The results of these studies suggest that high-dose therapy with autologous marrow support increases the proportion of patients with long-term survival without evidence of disease. Newer supportive care approaches with recombinant growth factors and mobilized peripheral blood cells and recurrent high-dose therapy cycles of non-cross resistant regimens may improve outcome further in these diseases and increase the application to more resistant tumors. The controversy about the importance of and the unexpected high frequency of marrow contamination is outlined.

Antineoplastic Combined Chemotherapy Protocols↗