PubMed Health⌕ Search

Biomedical subjects

R H Herzig

Publications and source records attributed to R H Herzig.

At least 37 records · Page 2Linked to original sources
PubMed1996

Dose-intensive chemotherapy with etoposide-cyclophosphamide for advanced breast cancer. North American Marrow Transplant Group.

Bone marrow and extensive bone involvement have limited the use of chemotherapy with stem cell support for treatment of women with metastatic breast cancer. The toxicity and efficacy of dose-intensive chemotherapy were studied using etoposide and cyclophosphamide without a stem cell support regimen for women with advanced breast cancer. The regimen was well tolerated, with treatment-related mortality similar to dose-intensive therapy with stem cell support. The overall 58% response rate is comparable to the response rate with dose-intensive chemotherapy regimens using stem cell support. The extent of disease, responsiveness to standard therapy, and dose of etoposide affected the response rate. Hematopoietic recovery was fairly prompt and was generally unaffected by the use of hematopoietic growth factors or the presence of breast cancer cells in the marrow. The use of stem cells or recombinant human interleukin-3 (rhIL-3) in combination with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) resulted in some benefit in neutrophil recovery. It was concluded that in many women with advanced breast cancer, a dose-intensive regimen of etoposide and cyclophosphamide results in response or stabilization of disease. Hematopoietic recovery, particularly platelet recovery, may be accelerated by a combination of rhIL-3 and rhGM-CSF.

Adult↗
PubMed1996

High-dose ara-C in older adults with acute leukemia.

The concept of high-dose ara-C (HIDAC) was introduced 15 years ago. Phase I studies established a maximum tolerated dose of 3 g/m2, given every 12 hours for 12 doses. Because dermatologic, gastrointestinal, and central nervous system toxicities were dose-limiting in patients over age 50, a reduction from the maximal dose was suggested. Initial studies with refractory or resistant acute myelogenous leukemia (AML), with or without anthracyclines, demonstrated a significant antileukemic effect of HIDAC, with about 60 percent of patients achieving a complete response. Studies by our group and others have established that older patients can be successfully treated with HIDAC, probably with some added benefit in combining dose-intensive regimens.

Age Factors↗
PubMed1996

Risk factors for hepatic veno-occlusive disease following HLA-identical sibling bone marrow transplants for leukemia.

The objective was to analyze risk factors for veno-occlusive disease of the liver (VOD) after allogeneic bone marrow transplantation. A cohort of 1717 recipients of HLA-identical sibling transplants for leukemia between 1988 and 1990, in 200 transplant teams worldwide, was studied. Patients were scored as having VOD if liver tissue showed typical histologic features or if they had all three of the following: (1) jaundice; (2) hepatomegaly and right upper quadrant abdominal pain; and (3) ascites and/or unexplained weight gain. Patients surviving more than 7 days post-transplant without histologic or any of these clinical features of VOD were classified as not having VOD. Patient-, disease- and transplant-related characteristics of 95 patients with VOD were compared to those of 1514 without VOD. Variables correlated with an increased risk of VOD were: pretransplant conditioning with busulfan and cyclophosphamide compared to total body radiation (relative risk (RR) 2.8; P < 0.0001), pretransplant fungal infection (RR 4.1; P = 0.011), pretransplant Karnofsky performance score < 90% (RR 1.9; P = 0.012), prior liver disease (RR 1.9; P = 0.05) and age > 20 years (RR 1.8; P = 0.05). In patients receiving radiation for conditioning, intravenous immune globulin decreased VOD risk (RR 0.26; P = 0.003). This analysis identifies risk factors for VOD. The data suggest several strategies for modifying transplant regimens to reduce VOD risk and which patients might be suitable subjects for trials of strategies of VOD prevention.

Acute Disease↗
PubMed1996

HLA-identical sibling bone marrow transplants vs chemotherapy for acute myelogenous leukemia in first remission.

There is controversy whether adults with acute myelogenous leukemia (AML) in first remission are best treated with chemotherapy or an HLA-identical sibling bone marrow transplant. We studied 1097 adults, 16-50 years old, with AML in first remission. Results of transplants from HLA-identical siblings reported to the International Bone Marrow Transplant Registry (IBMTR; n = 901) were compared with results of chemotherapy in comparable persons treated by the German AML Cooperative Group (GAMLCG; n = 196). Preliminary analyses identified subject- and disease-related variables differing between the cohorts and associated with treatment outcome within each cohort. We adjusted for these variables and differences in time-to-treatment in subsequent comparisons of treatment-related mortality, relapse, survival and leukemia-free survival (LFS). Five-year probability of treatment-related mortality was greater for transplants than chemotherapy (43% (95% confidence interval, 37-49%) vs 7% (3-11%); P< 0.0001). Five-year relapse probability was less for transplants than chemotherapy (24% (20-28%) vs 63% (55-71%); P< 0.0001). Five-year probability of survival was similar with transplants and chemotherapy (48% (43-53%) vs 42% (33-51%); P = 0.24). Five-year LFS probability was higher for transplants than chemotherapy (46% (42-50%) vs 35% (28-41%); P= 0.01). These data indicate that bone marrow transplants from HLA-identical siblings result in comparable survival but greater LFS than chemotherapy in adults with AML in first remission.

Adolescent↗
PubMed1995

High-dose etoposide, cyclophosphamide, and total body irradiation with allogeneic bone marrow transplantation for patients with acute myeloid leukemia in untreated first relapse: a study by the North American Marrow Transplant Group.

Relapse is a major cause of treatment failure following allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML). To reduce the risk of relapse following BMT for patients with hematologic malignancy, our group developed a novel preparative regimen which combines high-dose etoposide with cyclophosphamide and total body irradiation (VPCyTBI). We now report the outcome of therapy with VPCyTBI followed by allogeneic BMT for 40 patients with AML in untreated first relapse. With the exception of increased stomatitis, the toxicity of this regimen was similar to that reported by others for CyTBI. Forty-four months after transplant the actuarial probabilities of disease-free survival (DFS), persistent or recurrent leukemia, and transplant related mortality were .29, .44, and .47 respectively. DFS was improved (P < .01) and risk of persistent or recurrent leukemia reduced (P = .005) among patients with significant (grade > or = 2) acute GVHD. Patients with 30% or more blasts on pre-BMT bone marrow examination were not at increased risk for persistent or recurrent leukemia. We conclude that VPCyTBI with allogeneic BMT is effective therapy for AML in untreated first relapse and that a randomized trial comparing this regimen with CyTBI is warranted.

Actuarial Analysis↗
PubMed1993

Choice of pretransplant treatment and timing of transplants for chronic myelogenous leukemia in chronic phase.

We analyzed the outcome of 450 HLA-identical sibling bone marrow transplants for chronic myelogenous leukemia (CML) in chronic phase performed between 1985 and 1990 and reported to the International Bone Marrow Transplant Registry (IBMTR). All patients received either hydroxyurea (n = 292) or busulfan (n = 158) to treat their CML before transplant. The median interval between diagnosis and transplant was 10 months (range, 1 to 191). Patients treated with hydroxyurea had a higher probability (95% confidence interval) of leukemia-free survival (LFS) at 3 years than those treated with busulfan (61% [51% to 70%] v 45% [36% to 55%], P < .0003). Probability of LFS was also higher in patients transplanted within 1 year of diagnosis (61% [53 to 68%] v 47% [38% to 57%], P < .001). After adjustment for patient and transplant covariables in a multivariate analysis, prior chemotherapy and duration of disease pretransplant were independently associated with LFS. These data support the use of hydroxyurea rather than busulfan and transplant within 1 year of diagnosis for patients with CML and an HLA-identical sibling.

Actuarial Analysis↗
PubMed1993

High-dose weekly intravenous immunoglobulin to prevent infections in patients undergoing autologous bone marrow transplantation or severe myelosuppressive therapy. A study of the American Bone Marrow Transplant Group.

OBJECTIVE: To determine whether intravenous immunoglobulin (IVIG) prevents severe infections during autologous bone marrow transplantation or equivalent high-dose myelosuppressive therapy. DESIGN: Randomized, stratified, nonblinded study. SETTING: Three tertiary care university hospitals. PATIENTS: One hundred seventy patients entered the study; 82 received IVIG and 88 were untreated controls. The study groups were similar for parameters capable of influencing the likelihood of infection. INTERVENTIONS: Intravenous immunoglobulin was given weekly at a dose of 500 mg/kg body weight from the initiation of cytotoxic therapy to the resolution of neutropenia. MEASUREMENTS: The development of bloodstream or other clinically proven infection, platelet use, and the development of alloimmunity to platelet transfusion. RESULTS: Clinical infection, bacteremia, and fungemia occurred in 43%, 35%, and 6% of the IVIG-treated patients and in 44%, 34%, and 9% of the control patients. Gram-positive bacteremia and gram-negative bacteremia occurred in 28% and 11% of the IVIG group and in 23% and 13% of the control group. Death due to infection occurred in 4.9% of IVIG recipients and in 2.3% of controls. None of these observations was statistically significant (P > 0.2). Survival to hospital discharge was achieved in 86.6% of the IVIG group and in 96.6% of the control group. The survival difference (10%; 95% CI, 1.7% to 18.3%; P = 0.02) was due to a higher incidence of regimen-related toxic death in the IVIG-treated group. CONCLUSIONS: The use of IVIG did not prevent infection. Fewer deaths occurred among controls due to a higher incidence of fatal hepatic veno-occlusive disease in patients receiving IVIG.

Adolescent↗
PubMed1993

Dose-related cutaneous toxicities with etoposide.

BACKGROUND: Cutaneous toxicities are seen frequently in association with administration of high doses, but not standard doses, of agents. With the increasing use of etoposide in dose-intensive regimens, cutaneous toxicities are appearing with increasing frequency. METHODS: A retrospective analysis of 145 patients treated with various doses of etoposide was conducted. RESULTS: This analysis revealed a statistically significant increase in the frequency of these toxicities at doses of 2400 mg/m2 and 4200 mg/m2, compared with doses of 1800 mg/m2. Intense, painful palmar erythema accompanied by bullae formation and desquamation occurred at the 4200 mg/m2 dose. Symptoms were controlled by a short course of corticosteroids. CONCLUSION: Although they are not dose limiting, substantial dose-related skin toxicities can be an important side effect of high-dose etoposide therapy.

Dose-Response Relationship, Drug↗
PubMed1993

Techniques of harvesting and cryopreservation of stem cells.

Improved marrow processing techniques and in vitro marrow manipulations are revolutionizing the clinical application of both allogeneic and autologous bone marrow transplantation. The rapid evolution of clinically useful laboratory techniques now necessitates more sophisticated laboratory support of bone marrow transplantation.

Bone Marrow Purging↗
PubMed1992

Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia.

Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) has a poor prognosis when treated with conventional chemotherapy. We analyzed the outcome of 67 HLA-identical sibling bone marrow transplants (BMTs) for Ph1-positive ALL reported to the International Bone Marrow Transplant Registry (IBMTR). Twenty-one of 67 (31%) transplant recipients survived in continuous complete remission more than 2 years after transplant. Two-year actuarial probabilities (95% confidence interval) of leukemia-free survival were 38% (23% to 55%) for 33 patients transplanted in first remission, 41% (23% to 61%) for 22 patients transplanted after relapse, and 25% (9% to 53%) for 12 patients failing to achieve remission with conventional chemotherapy. These data indicate that transplants are effective treatment for Ph1-positive ALL.

Adolescent↗
PubMed1992

Should HLA-identical sibling bone marrow transplants for leukemia be restricted to large centers?

There is substantial evidence that the volume of medical procedures in a hospital has an inverse relationship with mortality. We analyzed data for 1313 recipients of HLA-identical sibling bone marrow transplants for early leukemia (acute leukemia in first remission or chronic myelogenous leukemia in first chronic phase) to determine whether transplant outcome differed in small and large centers. Transplants were performed in 86 bone marrow transplant centers active between the years 1983 and 1988, which participated in the International Bone Marrow Transplant Registry. Twenty-one (24%) centers performed five or fewer allogeneic transplants per year during the study period; five (6%) performed more than 40 per year. After adjustment for differences in patient and disease characteristics, the relative risks of treatment-related mortality (1.53, P less than .01) and treatment failure (1.38, P less than .04) were higher among patients who received transplants at centers doing five or fewer transplants per year than among those at larger centers. Among patients receiving transplants in centers performing more than five transplants a year, there was no statistically significant correlation between number of transplants and outcome.

Adult↗
PubMed1992

Encephalopathy and seizures induced by intravesical alum irrigations.

Hemorrhagic cystitis is a significant toxic effect of cyclophosphamide therapy. Continuous bladder irrigation of a 1% alum solution is a simple and generally safe method of chemical cautery to treat the bleeding urothelium. We report four cases of encephalopathy coincident with elevated aluminum levels as well as one patient who developed seizures while receiving continuous bladder irrigations with alum. All patients had significant renal insufficiency. We recommend the cautious use of alum irrigation in patients with renal impairment and monitoring of serum aluminum levels to prevent excessive accumulation and toxicity.

Administration, Intravesical↗
PubMed1992

Second HLA-identical sibling transplants for leukemia recurrence.

We analysed data from 114 recipients of HLA-identical sibling transplants who relapsed and received a second transplant between 1978 and 1989. Twenty-nine patients had acute lymphoblastic leukemia, 46 acute myeloid leukemia and 39 chronic myelogenous leukemia. Median (range) interval between first and second transplants was 15 (1-80) months. Following the second transplant, graft failure occurred in 2%, acute graft-versus-host disease (GVHD) in 27% and chronic GVHD in 21% of patients at risk. Risks of interstitial pneumonia and hepatic veno-occlusive disease were higher after the second than the first transplant. Two-year probabilities (95% confidence interval) of treatment-related mortality, relapse and leukemia-free survival were 41% (30-53%), 65% (53-75%) and 21% (14-30%), respectively. Leukemia-free survival was 7% (2-19%) among patients relapsing less than 6 months after their first transplant, with high rates of both relapse, 77% (49-92%), and treatment-related mortality 69% (46-85%). In contrast, leukemia-free survival was 28% (19-41%) in those relapsing more than 6 months after the first transplant; in this group the probability of relapse was 59% (45-72%) and treatment-related mortality 30% (20-43%). Factors correlated with better outcome included a diagnosis of chronic myelogenous leukemia, relapse more than 6 months after the first transplant, acute leukemia in remission prior to the second transplant and good performance status.

Adolescent↗
PubMed1992

The role of autologous bone marrow transplantation in the treatment of solid tumors.

Until effective new agents can be developed, increasing dose intensity may be the best way to improve therapy for patients who fail conventional treatment. Alkylating agents, including radiation, are likely candidates for use in dose-intensive combinations. Past phase I clinical trials of single agents have redefined the maximum tolerated doses when marrow transplantation attenuates the myelosuppression. High-dose combinations of more than two agents are only possible with significant dose reductions from single-agent maximum tolerated doses. Multiple courses of therapy might permit the use of more than two agents without dose reduction. A multidrug and/or multicourse approach will probably be needed to effect curative therapy.

Antineoplastic Agents↗
PubMed1991

High-dose cytarabine and daunorubicin induction and postremission chemotherapy for the treatment of acute myelogenous leukemia in adults.

Seventy consecutive adult patients with acute myelogenous leukemia (AML), median age 44 years, received high-dose cytarabine (3 g/m2 every 12 hours for 12 doses) followed by daunorubicin (45 mg/m2 daily for three doses) for remission induction. A single, identical course was planned for postremission therapy. Complete remission (CR) was achieved in 63 patients (90%, 95% confidence interval [CI] 83% to 97%), 60 after a single course. Eight patients were selected to undergo elective bone marrow transplantation (BMT) during first CR. Of the remaining 55 patients, 40 (73%) underwent planned post-CR therapy; 15 patients did not, owing to early relapse, excessive toxicity from the induction chemotherapy, or refusal. Nineteen patients, including 13 who received planned post-CR therapy, remain in continuous CR at a median follow-up of 5.2 years (range 3.0 to 7.1 years). The 5-year actuarial leukemia-free survival was 30% (95% Cl, 19% to 42%) for all patients achieving CR and 32% (95% Cl, 19% to 47%) for the 40 patients who received the planned post-CR chemotherapy. Analysis of various putative prognostic factors for CR and overall and leukemia-free survival showed significance for a previous history of myelodysplasia, higher initial leukocyte counts, certain French-American-British (FAB) types, and certain abnormal karyotypes. None of these factors was consistently significant regarding the above parameters, although small patient numbers in certain analyses may have obscured significant associations. Myelosuppression was occasionally prolonged after remission induction and especially post-CR therapy. Severe cerebellar toxicity was observed in 13 patients; in 11 cases, this toxicity was fully reversible. Other serious complications were infrequent. Intensive chemotherapy with high-dose cytarabine and daunorubicin has substantial antileukemic activity in adult AML, and may represent an improvement over conventional therapy. Relapses were common, however, even in patients who received planned therapy, and substantial toxicity was observed. The optimum use of this regimen in AML remains to be determined.

Adult↗
PubMed1991

High-dose etoposide and marrow transplantation.

Etoposide underwent conventional Phase I testing in the 1970s. The dose-limiting toxicity in these studies was mild myelosuppression; other toxicities were infrequent. If a greater degree of myelosuppression is accepted, higher than standard doses could be given. This approach takes advantage of the steep dose-response relationship for most chemotherapeutic agents, including etoposide, as shown in early in vitro and clinical studies. Thus, etoposide was considered an ideal agent for further dose-escalation studies, given its wide range of clinical antitumor activity at standard doses, steep dose-response curve, mild bone marrow suppression, and few nonmyeloid side effects. The high-dose etoposide studies that followed used improved and more intensive hematologic supportive care, including, in some trials, autologous marrow transplantation. When etoposide was used as a single agent in these high-dose trials, mucositis, and, to a lesser degree, hepatic dysfunction were dose-limiting. The maximum tolerated dose (MTD) in this setting was 2.4 to 3.0 g/m2. Multi-agent Phase I trials with etoposide and cyclophosphamide, total body irradiation, carmustine, or carboplatin also resulted in dose-limiting mucosal toxicity, with liver and lung problems appearing more often than with high-dose etoposide alone. The toxicity and MTD can be influenced markedly by the schedule of administration. Etoposide as a continuous intravenous infusion can be given at doses of 4.2 g/m2 (with 200 mg/kg cyclophosphamide) with similar toxicity, but without marrow support. The antitumor results in the lymphomas set the stage for treatment of solid tumors, where treatment of patients with "sensitive" relapses had the best outcome. Lymphoma patients had an 80% response rate; overall, long-term (greater than 2 years) disease-free survival was approximately 40%. Germ cell tumors were also responsive, and the same pattern of sensitive relapses and improvement in responding patients was seen (50% to 75% of patients greater than 1 year). In breast cancer and small cell lung cancer (SCLC), high-dose etoposide-containing regimens were used to intensify standard therapy. The results in these settings were not quite as good (breast cancer, 30% disease-free survival at 2 years; SCLC, 10% at 2 years).

Antineoplastic Combined Chemotherapy Protocols↗