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PubMed1982

Studies of DNA damage and cell death in embryonic limb buds induced by teratogenic exposure to cyclophosphamide.

Many teratologic investigations have shown that certain types of chemical insults to the embryo (those altering replication, transcription, and translation) can cause excessive cell death in tissues destined to become malformed. Chemical carcinogens also induce cell death in target tissues, but the critical event is believed to be heritable alteration in the DNA of surviving cells. In the present study, an attempt was made to study the interaction between cell death and DNA damage in the initiation of birth defects. The pattern of DNA damage induced by cyclophosphamide was examined at time intervals before, during, and after the necrotic episode in mouse embryo limb buds. The alkaline elution assay was used to measure alkali-labile sites in single-strand DNA due to its adaptability to small tissue samples. An ip dose of 20 mg/kg of cyclophosphamide induced forelimb malformations in 85% of surviving mouse fetuses and 30% embryolethality when administered at 9 am on Day 11. As early as 5 hr after exposure, a slight excess of necrosis was observed in treated limbs by light microscopy, while at 24 hr, massive necrosis was evident. By 48 and 72 hr, excess necrosis was not observed in treated limbs. When alkaline elution analysis was conducted at prenecrotic (1-, and 5-hr), necrotic (24-hr), and postnecrotic (48-, and 72-hr) intervals, a trend toward increasing DNA damage in treated limbs with time was observed. The greatest differences in elution values occurred during the postnecrotic period. Although mean retention values were not significantly different, significantly increased variance was obtained in retention values of treated limbs at all time intervals other than 1 hr. This may reflect the actual in vivo situation where relatively few cells within a heterogeneous population of cells carry sublethal DNA damage into the postnecrotic period. These results suggest that not all limb bud cells affected by teratogenic exposure to cyclophosphamide die, but that some persist to the postnecrotic period carrying heritable alterations in their DNA.

Abnormalities, Drug-Induced↗
PubMed2004

Ablation of hemophilic FVIII inhibitors with FVIII priming, cyclophosphamide immune suppression, and rapid tapering of FVIII immune tolerance.

The efficacy and toxicity of factor VIII (FVIII) priming, cyclophosphamide immune suppression, and rapid tapering of concurrent FVIII immune tolerance for subjects with hemophilic inhibitors were evaluated. Four subjects with hemophilic inhibitors were studied. Before treatment, inhibitors were present for a median of 8 months (mean 13 +/- 14.0 months). The median FVIII inhibitor titer was 16 BU/mL (mean 27.2 +/- 29.2 BU/mL). Following FVIII priming (80.0 +/- 70.2 U/kg), subjects received cyclophosphamide 1,418 +/- 636 mg/M2 i.v. q3 weeks for 4.4 +/- 1.7 courses. Subjects concurrently received a low (6 U/kg/day), moderate (30 U/kg/day), or high (100 U/kg/day) dose of FVIII followed by a rapid taper as the inhibitor titer decreased or resolved. During treatment, the inhibitor titer initially increased but then rapidly declined. Inhibitors resolved in 3.9 +/- 2.9 months. One inhibitor recurred at 2.8 years, but it was successfully re-treated. Effectiveness did not depend on the FVIII dose. Toxicity was minimal. Cyclophosphamide (1,400 mg/M2) administered after a priming dose of FVIII (80 U/kg) i.v. q3 weeks for 2-6 cycles with a rapid taper of concurrently administered daily FVIII as the inhibitor titer falls is an effective approach to hemophilic inhibitor ablation.

Adult↗
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↗
PubMed2003

Treatment of refractory myasthenia: "rebooting" with high-dose cyclophosphamide.

Patients with myasthenia gravis (MG) who do not respond to conventional immunotherapeutic agents, or cannot tolerate their side effects, are considered "refractory." Ablation of the immune system followed by bone marrow transplant has been shown to cure experimental MG in rats. It is now known that immunoablative treatment with high-dose cyclophosphamide does not damage hematopoietic "stem cells," permitting repopulation of the immune system without bone marrow transplant. Recent evidence indicates that this treatment can induce durable remissions in autoimmune diseases. We treated three myasthenic patients, for whom treatment with thymectomy, plasmapheresis, and conventional immunotherapeutic agents failed, by using high-dose cyclophosphamide (50mg/kg/day intravenously for 4 days) followed by granulocyte colony stimulating factor. All three patients tolerated the treatment well and have had marked improvement in myasthenic weakness, permitting reduction of immunosuppressive medication to minimal levels. Acetylcholine receptor (AChR) antibody levels decreased in two AChR antibody-positive patients, and anti-MuSK antibody levels decreased in one "AChR antibody-negative" patient. The patients have been followed for up to 3.5 years, with no recurrence of symptoms. High-dose cyclophosphamide treatment appears to be an effective and safe treatment for selected patients with refractory MG. Further follow-up of these and additional patients will be needed to determine whether the benefit is durable.

Adult↗
PubMed1989

Infectious complications of cyclophosphamide treatment for vasculitis.

Fifteen patients with Wegener's granulomatosis, polyarteritis nodosa, or isolated angiitis of the central nervous system were treated with cyclophosphamide according to a widely used regimen. Seventeen clinical episodes of infection were observed over 201 patient-months of cyclophosphamide therapy, and 2 patients died of pneumonia. Notably, neither the incidence of leukopenia nor the dosage or duration of cyclophosphamide or corticosteroid therapy correlated well with infection, which occurred most frequently in men over 60 years of age. Patients with Wegener's granulomatosis appeared to be at greater risk of infection than those with the other forms of vasculitis. These results suggest that this treatment regimen may not be as safe as was previously thought.

Adolescent↗
PubMed2003

Effects of oral cyclophosphamide and prednisolone therapy on the endothelial functions and clinical findings in patients with early diffuse systemic sclerosis.

OBJECTIVE: The endothelial damage of microvascular structures in systemic sclerosis (SSc; scleroderma) is associated with increased levels of endothelial adhesion molecules and endothelium-associated cytokines, including E-selectin and thrombomodulin. Although there is still no ideal specific pharmacologic therapy for SSc, cyclophosphamide has resulted in clinical improvement in patients with SSc-related active alveolitis. This study was designed to assess the expression of E-selectin and thrombomodulin in patients with early diffuse SSc, and to investigate the effects of oral cyclophosphamide combined with prednisolone therapy on the levels of these endothelium-associated cytokines and on the patients' clinical outcomes. METHODS: Thirteen patients with early diffuse SSc were treated with oral cyclophosphamide (2-2.5 mg/kg/day) and methylprednisolone (30 mg/every other day) for 1 year. The outcomes were determined as clinical (skin score) and laboratory parameters (including the erythrocyte sedimentation rate, complete blood cell count, levels of C-reactive protein, antinuclear antibody, anti-double-stranded DNA, rate of creatinine clearance, and findings on pulmonary function tests, esophageal manometry, and echocardiography). The concentrations of E-selectin and thrombomodulin were measured in the pretreatment and posttreatment serum samples from the SSc patients and from 12 healthy adults as controls. RESULTS: In the patients with early diffuse SSc, pretreatment and posttreatment mean levels of E-selectin were 51 ng/ml (range 34.2-135.5) and 33.4 ng/ml (range 23-62.5), respectively (P = 0.01), and those of thrombomodulin were 82 ng/ml (range 35.8-120.5) and 74.6 ng/ml (range 23.3-91.3), respectively (P = 0.016). Clinical and laboratory parameters (the skin score and measures of pulmonary function [forced vital capacity and diffusing capacity for carbon monoxide]) were also improved (P < 0.05 for each) at the end of the followup period. CONCLUSION: Combination therapy with cylophosphamide plus prednisolone is effective in the treatment of early diffuse SSc. Circulating levels of E-selectin and thrombomodulin not only demonstrate the extent of endothelial injury and/or activation, but also could be a useful marker to monitor the disease activity in SSc.

Administration, Oral↗
PubMedDate not supplied

Influence of cyclophosphamide and other immunosuppressive drugs on immune disorders and neoplasia in NZB/NZW mice.

NZB/NZW mice were treated with various immunosuppressive drugs used in human SLE. Cyclophosphamide (5 mg/kg 6 days out of 7), alone or with prednisolone, was better than azathioprine, prednisolone, or azathioprine-plus-prednisolone, in prolonging survival and/or reducing proteinuria, Coomb's antibodies, antinuclear antibodies, and glomerular deposits of gamma-globulin. Intermittent bolus therapy with cyclophosphamide (59 mg/kg/10 days) was as effective as daily therapy. However, 61% of the mice receiving any cyclophosphamide regimen developed malignant tumors compared to none in the other groups.

Animals↗
PubMed1981

Effect of cyclophosphamide, hydrocortisone and levamisole on collagen-induced arthritis in rats.

The immune response of rats to type II collagen was modified by pretreating the rats with levamisole, hydrocortisone, or cyclophosphamide. Rats were observed for the development of collagen-induced arthritis and were bled serially for the determination of antibody levels to type II collagen. Levamisole had a slight but not significant potentiating effect with arthritis developing earlier, whereas hydrocortisone and cyclophosphamide significantly depressed the incidence of arthritis; cyclophosphamide also delayed its onset. Antibody levels measured by radioimmunoassay paralleled the clinical course of arthritis.

Animals↗
PubMed1994

Improved pulmonary function in systemic sclerosis after treatment with cyclophosphamide.

OBJECTIVE: Pulmonary fibrosis is a common feature of systemic sclerosis (SSc) and a major cause of morbidity and mortality. Since alveolitis may be an essential step in the development of pulmonary fibrosis, we investigated the use of immunosuppressive drug therapy to improve pulmonary function in patients with SSc. METHODS: Eighteen patients with progressive pulmonary dysfunction, diminished vital capacity (VC), and/or decreased static lung compliance (Cst) were treated with cyclophosphamide and corticosteroids for 1 year. Eight patients had diffuse cutaneous SSc and 10 had limited cutaneous SSc. The median disease duration was 2.5 years (range 0.5-17 years). RESULTS: VC increased in 14 of 18 patients and the median VC rose from 74% to 80% of predicted. Cst improved in 8 of 12 patients and the median Cst increased from 59% to 66% of predicted. Pulmonary nonfibrotic opacities disappeared in 9 of 12 patients. The erythrocyte sedimentation rate (ESR) and serum concentrations of orosomucoid, C-reactive protein, and aminopropeptide type III collagen all improved. The patients were divided into 2 groups based on the presence or absence of elevations in acute-phase protein levels and ESR before therapy. Among the 12 patients with biochemical signs of inflammation, VC increased in 11, and Cst improved or was unchanged in 7 of the 8 who were tested. The median VC in this subgroup increased from 73% to 80% of predicted and the median Cst increased from 57% to 60% of predicted. In the group of 18 patients overall, the skin score decreased, while esophageal and renal function remained stable. CONCLUSION: Cyclophosphamide may have a beneficial effect on pulmonary fibrosis in patients with SSc and elevated levels of acute-phase proteins. Controlled trials of cyclophosphamide in pulmonary SSc should be performed and should focus on such patients.

Adult↗
PubMed1994

Immediate hypersensitivity reaction to cyclophosphamide.

We report a case of an acute anaphylactic reaction to intravenous cyclophosphamide in a patient with systemic lupus erythematosus. Skin testing for reactivity to cyclophosphamide and one of its metabolites, 4-hydroperoxycyclophosphamide, was performed on the patient and on 6 controls. The patient exhibited positive skin test responses; all controls had negative responses. The results suggest an acute hypersensitivity reaction related to sensitivity to cyclophosphamide and to 4-hydroperoxycyclophosphamide, through a shared antigenic determinant or dual sensitization.

Adult↗
PubMedDate not supplied

Disposition of cyclophosphamide in the rabbit and human cornea.

Rabbit (dark irides and albino) and human corneas were excised and mounted in a Lucite chamber in order to determine the permeability of cyclophosphamide-14C and to identify its metabolites. The chromatographic scans obtained from the developed thin-layer plates showed only one peak for either rabbit or human corneas which corresponded to cyclophosphamide. By measuring the permeability of cyclophosphamide across the intact cornea, stroma alone, epithelium/stroma, and stroma/endothelium, it was possible to determine the resistance to penetration for each layer. The epithelium was the rate determining barrier, whereas both the stroma and endothelium offered little resistance. The stroma behaves as an inert sieve with drug diffusing through an aqueous media of gel-like mucopolysaccharide interspersed by a matrix of collagen fibrils.

Animals↗
PubMed2005

Prior exposure to indole-3-carbinol decreases the incidence of specific cyclophosphamide-induced developmental defects in mice.

BACKGROUND: Indole-3-carbinol (I3C) is a product of the hydrolysis of glucobrassicin that is found in cruciferous vegetables. I3C can intervene in toxic processes that are mediated by oxidative mechanisms because it possesses the chemical and pharmacokinetic properties necessary to provide a free radical trap. Cyclophosphamide (CP) is a bifunctional alkylating agent known to produce DNA damage and to cause developmental toxicity, including malformations, in laboratory animals. METHODS: Pregnant CD-1 mice were given a 100 mg/kg dose of I3C 24 or 48 hr before administration of 20 mg/kg CP on gestation day 10 (GD 10). Controls were given the vehicle (DMSO), I3C, or CP. This regimen was carried out to determine if I3C could protect against the developmental toxicity of alkylating agents, such as CP. Dams were sacrificed on GD 17 and their litters were examined for adverse effects. RESULTS: Treatment with I3C 48 hr before CP administration was associated with decreased fetal limb and tail malformations. Limb malformation incidences were reduced from 42% litters affected in the CP control to 16% in the I3C/CP 48-hr treatment group, and tail malformations were reduced from 45% in the CP control to 16% in the I3C/CP 48-hr treatment group, indicating a protective effect of prior exposure to I3C. I3C given 24 hr before CP had no significant protective effect, while having an apparently adverse consequence with regard to the incidence of talipes. CONCLUSIONS: Exposure of a developing mammal to indole-3-carbinol before exposure to cyclophosphamide during organogenesis can influence the teratogenicity of cyclophosphamide.

Abnormalities, Drug-Induced↗
PubMed1994

The determination of cyclophosphamide and its metabolites in blood plasma as stable trifluoroacetyl derivatives by electron capture chemical ionization gas chromatography/mass spectrometry.

A method is described for the determination of the antitumour drug cyclophosphamide and six stable metabolites in plasma of cancer patients, namely dechloroethyl-cyclophosphamide, 4-keto-cyclophosphamide, carboxy-phosphamide, alcophosphamide, nor-nitrogen mustard and the N-chloroethyl-1,3-oxazolidine-2-one, as methyl and/or trifluoroacetyl derivatives by single ion monitoring gas chromatography/mass spectrometry, mostly in the electron capture chemical ionization mode. The isolation of most metabolites was performed by solid-phase C-18 extraction in weakly acidic medium. The phosphoramide mustard isolated under these conditions decomposes readily to the nor-nitrogen mustard during derivatization. The original nor-nitrogen mustard and the chloroethyl-1,3-oxazolidine-2-one were isolated by liquid extraction with ethyl acetate in alkaline medium. Recoveries of 75-99% were measured using spiked blank plasma samples. Quantitation of metabolites in patient plasma samples was performed using two sets of calibration curves for the concentration ranges of 1-100 ng and 0.1-10 micrograms of metabolite per millilitre of original plasma.

Antineoplastic Agents↗
PubMed2003

Phase II study of cladribine and cyclophosphamide in patients with chronic lymphocytic leukemia and prolymphocytic leukemia.

BACKGROUND: One of the mechanisms of action of cladribine is the inhibition of DNA repair of damage caused by radiation, alkylating agents, or other drugs. To determine its antitumor activity in combination with cyclophosphamide, we initiated a Phase II trial of the two agents in patients with advanced chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL). METHODS: Twenty-nine patients with refractory or recurrent CLL or PLL received cladribine 4 mg/m(2)/day and cyclophosphamide 350 mg/m(2)/day (both administered intravenously) for 3 days every 4 weeks. RESULTS: Eleven patients (38%), nine with CLL and two with PLL, had a response. The median duration of response was 12 months. Severe extrahematologic toxicity (National Cancer Institute Grade 3-4) occurred in two patients, consisting of skin rash in one patient and progressive multifocal leukoencephalopathy in the other. The most common form of hematologic toxicity was severe neutropenia, which developed after 25% of the 84 courses was administered. Severe thrombocytopenia and anemia developed after 12% and 7% of the courses, respectively, and five episodes of anemia were immunomediated. In addition, three major infections resulted in the death of one patient. CONCLUSIONS: Although inferior to the combination fludarabine plus cyclophosphamide, this regimen showed interesting activity in patients with advanced CLL or PLL. Myelosuppression was the major dose-limiting toxic effect.

Adult↗
PubMed2003

Phase II trial of oral cyclophosphamide, prednisone, and diethylstilbestrol for androgen-independent prostate carcinoma.

BACKGROUND: The authors evaluated the combination of oral cyclophosphamide, oral prednisone, and diethylstilbestrol (DES) in patients with androgen-independent prostate carcinoma (AIPC). METHODS: Thirty-seven patients with prostate carcinoma refractory to androgen ablation who had undergone antiandrogen withdrawal (if previously treated with an antiandrogen) were enrolled in the current study. They were treated with oral cyclophosphamide 100 mg per day on Days 1-20, prednisone 10 mg per day continuously, and DES 1 mg continuously, on a 30-day cycle. Warfarin 1 mg per day was given as prophylaxis for thrombosis. Patient levels of prostate-specific antigen (PSA) were monitored on a monthly basis, with imaging studies every 3 months. Patients continued to receive therapy until disease progression or the occurrence of significant toxicity. The effect of therapy on the patient's quality of life was assessed using the Functional Assessment of Cancer Therapy-Prostate. RESULTS: Thirty-six patients were evaluable for response. Of the 36 patients, 15 (42%) had a 50% or greater decline in PSA levels from pretreatment levels and 1 patient (6%) with measurable disease had a partial response to therapy. The median duration of response was 4.5 months (range, 4-18 months). The overall median survival period was 16.4 months. The treatment was well tolerated, with only three patients removed from the study for toxicities associated with treatment. One patient, who had been treated for more than 24 months, developed acute leukemia. Quality of life evaluation in 17 patients showed a significant improvement in responders, whereas nonresponders had no deterioration while receiving therapy. CONCLUSIONS: Cyclophosphamide, prednisone, and DES represent a well tolerated, low-cost combination therapy with significant activity in the treatment of patients with AIPC.

Administration, Oral↗
PubMed2003

Metronomic therapy with cyclophosphamide and dexamethasone for prostate carcinoma.

BACKGROUND: The current study was designed to evaluate the efficacy and toxicity of the continuous oral administration of a combination of cyclophosphamide (50 mg/day given in the morning) and dexamethasone (1 mg/day given in the evening) in patients with prostate specific antigen (PSA) progression despite single or multiagent hormone therapy and antiandrogen withdrawal. METHODS: The authors retrospectively evaluated the medical records of all patients with prostate carcinoma who were treated with dexamethasone and cyclophosphamide and who were unable to participate in Phase II drug trials or had failed previous chemotherapy regimens. RESULTS: Using clinical response guidelines set forth by the Prostate Specific Antigen Working Group, 29% of patients were found to have a > or = 80% reduction in PSA, 39% were found to have a 50-79% reduction in PSA, 6% were found to have a < 50% decrease in PSA, and 26% experienced disease progression while receiving treatment. The duration of response was 8 months (95% confidence interval [95% CI], 4-10 months). The duration of treatment was 9 months (95% CI, 6-14 months). The treatment was reported to be well tolerated with side effects being primarily bruising, Cushingoid facies, and gastrointestinal distress. CONCLUSIONS: In the current study, low-dose dexamethasone and cyclophosphamide demonstrated efficacy as salvage therapy in the treatment of patients with hormone-refractory prostate carcinoma.

Aged↗
PubMed2004

Long-term follow-up of patients with intermediate or high-grade non-Hodgkin lymphoma treated with a combination of cyclophosphamide, epirubicin, vincristine, and prednisone.

BACKGROUND: Doxorubicin cardiotoxicity is one of the most serious side effects of the cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, regimen, especially among elderly patients. In the CEOP regimen, epirubicin was substituted for doxorubicin to reduce cardiotoxicity. METHODS: Between March 1984 and September 1998, 186 previously untreated patients with a histologically confirmed diagnosis of intermediate- or high-grade non-Hodgkin lymphoma according to the Working Formulation were treated with CEOP (cyclophosphamide, 750 mg/m(2), epirubicin, 75 mg/m(2), vincristine, 1.4 mg/m(2); and prednisone, 60 mg per day orally on Days 1-5). Of 186 patients, 85 (45.7%) had Stage IV disease, and 60 (32.3%) had an International Prognostic Index score > 2. Comorbidity was present in 36 patients (19.3%). RESULTS: Complete remission (CR) was achieved in 119 patients (64.3%), and partial remission was achieved in 30 patients (16.2%). Among the patients who achieved a CR, 95 (79.8%) were still disease free at a median follow-up time of 86.9 months (range, 14-200 months). The remaining 24 patients experienced disease recurrence, at a median follow-up time of 19 months (range, 3-101 months). The relative dose intensities were 0.69, 0.89, and 0.80 for vincristine, epirubicin, and cyclophosphamide, respectively. Two patients died of toxicity due to infection. Two patients, 59 and 73 years old, respectively, experienced arrhythmia. Another patient, age 64 years, who had a myocardial infarction 10 years earlier, had angina. One patient with hypertension experienced cardiac failure. No patients died of cardiac toxicity. CONCLUSION: Long-term follow-up confirmed that CEOP is an effective and well-tolerated chemotherapy regimen for intermediate- and high-grade lymphoma. The results were promising, especially among elderly patients.

Adolescent↗
PubMed2006

Four versus six courses of a dose-escalated cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen plus etoposide (megaCHOEP) and autologous stem cell transplantation: early dose intensity is crucial in treating younger patients with poor prognosis aggressive lymphoma.

BACKGROUND: Patients with aggressive lymphoma and high-risk features at the time of diagnosis are reported to have a poor prognosis with standard therapy. Attempts to improve the results achieved with the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) using second-generation or third-generation chemotherapy have failed. In the current study, the authors increased the doses and dose intensity of drugs used for the conventional first-line therapy of aggressive lymphoma and designed a Phase II randomized trial that compared four and six courses of dose-escalated CHOP plus etoposide (megaCHOEP) supported by the transplantation of peripheral blood stem cells. METHODS: Eighty-four patients age < 60 years with aggressive lymphoma and elevated lactate dehydrogenase (LDH) levels were randomized to receive either 4 (Arm A) or 6 (Arm B) courses of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (megaCHOEP). The last three treatment courses were supported by autologous peripheral blood stem cell transplantation. Although the total doses of cyclophosphamide and etoposide were comparable, the dose intensity during the first 3 treatment courses was planned to be 2.8-fold and 2.0-fold higher, respectively, for patients in Arm A. RESULTS: Thirty-seven patients in Arm A (90.2%) but only 18 patients in Arm B (69.2%) were able to complete therapy (P = 0.048). The complete response rate was 65.8% in Arm A and 50.0% in Arm B; the disease recurrence rates were 18.5% versus 61.5% (P = 0.011). Freedom from treatment failure at 2 years was 52.5% (95% confidence interval [95% CI], 36.9-68.2%) in Arm A and 23.1% (95% CI, 6.9-39.3%) in Arm B (P = 0.02). The overall survival rate was 70% (95% CI, 54.9-85.0%) in Arm A and 46.2% (95% CI, 27.0-65.3%) in Arm B (P = 0.037). CONCLUSIONS: The results of the current study demonstrate that dose intensity, in particular early dose intensity, significantly influences disease control with high-dose therapy (HDT) and autologous stem cell transplantation. These results also may explain the failure of HDT with low early dose intensity to improve the results obtained with conventional chemotherapy.

Adult↗