			Home About us Contact

High-dose Cyclophosphamide (high-dose + cyclophosphamide)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

High-dose cyclophosphamide versus monthly intravenous cyclophosphamide for systemic lupus erythematosus: A prospective randomized trial,

ARTHRITIS & RHEUMATISM, Issue 5 2010
Michelle Petri
Objective Monthly intravenous (IV) cyclophosphamide for 6 months has been the standard induction regimen for lupus nephritis, followed by a maintenance regimen of quarterly infusions for 2 years. We undertook this study to compare the efficacy and safety of the standard regimen versus a high-dose IV cyclophosphamide regimen. Methods We performed a prospective randomized trial comparing monthly IV cyclophosphamide at 750 mg/m2 body surface area for 6 months followed by quarterly IV cyclophosphamide for 2 years (traditional treatment) against high-dose IV cyclophosphamide (50 mg/kg daily for 4 days) (high-dose treatment). Entry criteria included renal lupus, neurologic lupus, or other organ system involvement with moderate-to-severe activity. Results Fifty-one patients were randomized; 3 withdrew before treatment and 1 committed suicide after 2 months of high-dose treatment. Twenty-two had renal lupus, 14 had neurologic lupus, and 11 had other organ involvement. The outcome measure was the Responder Index for Lupus Erythematosus (complete response, partial response, no change, or worsening). At 6 months (the end of induction), 11 of 21 patients (52%) in the high-dose treatment group had a complete response compared with 9 of 26 patients (35%) in the traditional treatment group (P = 0.13). At the final visit (30 months), 10 of 21 patients (48%) in the high-dose treatment group had a complete response compared with 13 of 20 patients (65%) who continued with traditional treatment (P = 0.13). Six patients crossed over from traditional treatment to high-dose treatment because of lack of response, and 3 of those patients became complete responders. Conclusion There was not strong evidence that monthly IV cyclophosphamide and high-dose IV cyclophosphamide differed in complete or in any (complete or partial) response to induction or maintenance therapy. However, nonresponders to monthly IV cyclophosphamide can sometimes be rescued with high-dose IV cyclophosphamide. [source]

High-dose cyclophosphamide does not eradicate paroxysmal nocturnal haemoglobinuria haematopoiesis in mice carrying a Piga gene mutation

BRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2003
Anne Schaefer
Summary. Recently, high-dose cyclophosphamide (HD CY) has been used in the treatment of aplastic anaemia. Several reports have suggested that the treatment may either eradicate or suppress mutant clonal haematopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH). We therefore treated mice that have a proportion of blood cells deficient in GPI-anchor molecules (PIGA,) with HD CY, and monitored their peripheral blood counts during and after treatment. HD CY produced a transient myelosuppression; however, the contribution of PIGA, haematopoiesis to the peripheral blood remained unchanged, suggesting that HD CY is unlikely to eliminate an existing PNH clone in patients treated for aplastic anaemia. [source]

Ifosfamide, etoposide, cytarabine, and dexamethasone as salvage treatment followed by high-dose cyclophosphamide, melphalan, and etoposide with autologous peripheral blood stem cell transplantation for relapsed or refractory lymphomas

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2007
P. Schütt
Abstract High-dose chemotherapy (HD-CT) with autologous stem cell transplantation is considered to be the treatment of choice for relapsed high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) patients, but the optimal treatment has not yet been defined. We evaluated a salvage treatment regimen consisting of conventional cycles with ifosfamide, etoposide, cytarabine, and dexamethasone (IVAD) followed by two cycles of HD-CT consisting of cyclophosphamide, melphalan, and etoposide (CMV) with autologous stem cell support in patients with relapsed or refractory NHL (n = 59) and HL (n = 16). Response to IVAD was complete remission (CR) in 16 patients (21%), partial remission (PR) in 39 patients (52%), stable disease (SD) in 18 patients (24%), and progressive disease (PD) in two patients (2.7%). Of 70 patients treated with HD-CT, 41 patients (59%) showed a CR, 20 patients a PR (29%), eight patients a SD (11%), and one patient a PD (1.4%). The 5-yr overall survival for the entire group of patients was 29%, and for patients with NHL and HL 25%, and 38%, respectively. The respective event-free survival probabilities at 5 yr were 22%, 16%, and 31%. Seven treatment-related deaths due to septicemia (three), cardiac arrhythmia (one), pneumonia (one), pneumonitis (one), and toxic epidermal necrolysis (one) were observed. In multivariate analysis, an International Prognostic Index of ,2 and resistant disease to first-line chemotherapy were poor independent prognostic factors for the subgroup of patients with NHL. In conclusion, these results indicate that IVAD/CMV is feasible as a salvage therapy for lymphoma patients. This treatment is currently evaluated with the addition of rituximab. [source]

Monitoring of cardiac function by serum cardiac troponin T levels, ventricular repolarisation indices, and echocardiography after conditioning with fractionated total body irradiation and high-dose cyclophosphamide

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2002
H.W. Auner
Abstract:Objectives : Highly differing rates of cardiac complications associated with high-dose cyclophosphamide (CY) have been reported, and only one clinical study has been performed on the cardiotoxic effects of CY monotherapy following total body irradiation (TBI). Patients and methods : We prospectively evaluated the potential cardiotoxic effects of conditioning with fractionated total body irradiation and high-dose cyclophosphamide (TBI/CY) by serial measurement of serum cardiac troponin T (cTnT), assessment of systolic and diastolic echocardiographic parameters and analysis of ventricular repolarisation indices (QT-dispersion and corrected QT-dispersion) in 30 adult patients with haematological malignancies undergoing haematopoietic stem cell transplantation. Results: There was no evidence of pretreatment cardiac dysfunction in any patient. Although cTnT was determined serially for a median of 14 d after completion of conditioning, no elevated levels were observed. Echocardiographic parameters did not show any significant change at a median follow-up of 5 months except for one patient with evidence of impaired diastolic filling. No significant differences for mean values before and after high-dose CY were noted for ventricular repolarisation indices. Two patients had a significant increase in corrected QT-dispersion after CY without any other signs of cardiotoxicity. Congestive heart failure or arrythmias were not observed. Conclusions : These data suggest that TBI/CY is safe with respect to cardiotoxicity in patients without pre-existing cardiac dysfunction. Hitherto unknown synergistic cardiotoxic effects of CY with other cytostatic drugs may constitute the major pathogenic factor of myocardial dysfunction after high-dose chemotherapy. [source]

Mobilisation of tumour cells along with CD34+ cells to peripheral blood in multiple myeloma

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5-6 2001
Lene Meldgaard Knudsen
Abstract:Background: Cells belonging to the malignant clone are found in the peripheral blood in myeloma patients. In order to minimise the content of tumour cells in the stem cell product it is crucial to perform stem cell harvest at a time when tumour cells in the peripheral blood are at a minimum. Objective: The aim of the study was to compare the mobilisation kinetics of normal CD34+ cells and myeloma plasma cells during mobilisation with either G-CSF alone or high-dose cyclophosphamide (HDCy) plus G-CSF. Design and methods: Morning blood samples were drawn each day during mobilisation from start of G-CSF or HDCy and to the end of leukapheresis, and were analysed by flow cytometry for content of CD34+ cells and myeloma plasma cells (CD38+ + CD45,). Tumour cells were also estimated by a patient-specific real-time polymerase chain reaction (PCR) method based on the 5, nuclease TaqMan technology. Results: Flow cytometry data from 16 patients showed concomitant mobilisation of CD34+ cells and myeloma plasma cells. Seven patients were mobilised twice; first with G-CSF alone and then with HDCy plus G-CSF. There was no difference between the two mobilisation regimens regarding tumour cell mobilisation kinetics. Real-time PCR was performed in one patient and confirmed the mobilisation of tumour cells at the time when CD34+ blood cells were at a maximum. Conclusions: Tumour cells are mobilised to the peripheral blood at the same time as CD34+ cells in multiple myeloma patients after priming with both G-CSF alone and HDCy in combination with G-CSF. [source]

Low cost autologous peripheral blood stem cell transplantation performed in a municipal hospital for a patient with plasma cell leukaemia

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2002
K. Ghosh
Autologous peripheral blood stem cell transplantation (PBSCT) is a costly procedure. In India, the cost varies from US$20 000 to 25 000 and most patients cannot afford it. Using several cost-cutting measures, we were able to treat a patient with plasma cell leukaemia by autologous PBSCT. A 42-year-old-male presented with plasma cell leukaemia. He was treated with VAD therapy, followed by high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) for mobilization of peripheral blood stem cells. The patient was conditioned with high dose melphalan, followed by autologous PBSCT. The procedure was performed in a municipal hospital in which there was no prior experience with stem cell transplantation. Costs were reduced by: (i) using oral medication whenever possible; (ii) having a relative of the patient prepare his food under medical guidance; (iii) starting G,CSF on day 7 rather than on day 1; (iv) short-term storage of the PBSC in an ordinary refrigerator at 4 °C without cryopreservation; (v) infusing a large number of CD34+ cells, which shortened the time to engraftment; (vi) delegating many of the functions of a marrow transplant nurse to a resident physician. The cost of transplantation was thereby reduced to about US$ 6000, with successful engraftment by day +13. The patient remained in remission for 7 months, after which he relapsed and was treated with chemotherapy and electron beam radiation to the skin. [source]

Synchronised therapy and high-dose cyclophosphamide in proliferative lupus nephritis

JOURNAL OF CLINICAL APHERESIS, Issue 2 2002
Maria Giovanna Danieli
Abstract The aim of this open study was to compare the outcomes and side effects of plasmapheresis (PP) in patients with proliferative lupus nephritis treated with cyclophosphamide (Cyc) boluses. The study involved 28 consecutive patients. All of the patients met the ACR modified criteria for SLE and underwent a qualifying renal biopsy. In group I, patients were treated with synchronised therapy (PP, 50 ml/kg, followed by pulse Cyc, 750 mg/m2, repeated monthly for 6 months), whereas in group II, they were given only intermittent Cyc boluses (at the same dosage). The data were collected in the patients' records according to a standardised protocol. Patients were followed-up for a mean of 4 years. The disease-free survival was analysed using Kaplan-Meier estimated survival curves ([S(t)]). At the end of the 6-month treatment period, a statistically significant number of patients in group I (75%) was in complete remission in comparison to group II (31%) (P < 0.02), whereas at long-term follow-up, these percentages were similar (41% vs. 50%, P = n.s.). The main functional and immunological parameters showed a normalisation in both groups. The risk of a poor renal outcome significantly correlated with high serum creatinine levels at the onset of nephritis (P < 0.05). We documented a higher rate of infectious complications in group I. This study reports that synchronised therapy is useful in inducing a faster remission in patients with proliferative lupus nephritis. However, it is not superior to conventional therapy at long term follow-up analysis. Positive results should be reinforced by a long-term maintenance therapy. J. Clin. Apheresis 17:72,77, 2002. © 2002 Wiley-Liss, Inc. [source]

High-dose cyclophosphamide does not eradicate paroxysmal nocturnal haemoglobinuria haematopoiesis in mice carrying a Piga gene mutation

Complete response in multiple myeloma

CANCER, Issue 9 2006
Clinical trial E948, an Eastern Cooperative Oncology Group study not involving stem cell transplantation
Abstract BACKGROUND The importance of obtaining a complete response (CR) in multiple myeloma (MM) treated with chemotherapy is unclear. METHODS The Eastern Cooperative Oncology Group evaluated 653 previously untreated patients with active MM randomized to vincristine, carmustine (BCNU), melphalan, cyclophosphamide, and prednisone (VBMCP), to VBMCP and recombinant interferon alfa-2 (INF,-2), or to VBMCP and high-dose cyclophosphamide. RESULTS Objective response was achieved in 420 (67%) of the 628 eligible patients, and 85 (14%) achieved a CR. Patients receiving VBMCP and recombinant INF,-2 had a significantly higher CR (18%) than those receiving VBMCP alone (10%) (P = .02). The CR rate for VBMCP and high-dose cyclophosphamide was 12%. Median duration of survival was 3.5 years for all eligible patients, and the estimated 5-year survival rate was 31%. The median duration of survival from the date of objective response was 5.1 years for those who achieved a CR and 3.3 years for those with a partial response (P < .0001). The median postresponse survival was 6.6 years in the 21 patients in CR with nonclonal disease and 4.4 years in the 11 patients in CR who had persistent clonal disease. All patients with negative immunofixation results and nonclonal plasma cells in whom polymerase chain reaction was performed had a positive result (presence of tumor DNA). CONCLUSION Patients in whom a CR was achieved had a longer survival than those who had a partial response. Cancer 2006. © 2006 American Cancer Society. [source]

Quality of life among patients with Stage II and III breast carcinoma randomized to receive high-dose chemotherapy with autologous bone marrow support or intermediate-dose chemotherapy,,

CANCER, Issue 8 2005
Leukemia Group B 906, Results from Cancer
Abstract BACKGROUND The objective of this study was to compare the quality of life (QOL) after treatment among patients who had breast carcinoma with multiple positive lymph nodes. The patients were randomized to receive either high-dose chemotherapy with autologous stem cell support (HDC) or intermediate-dose chemotherapy (IDC) in the adjuvant setting. METHODS Two hundred forty-six patients with AJCC Stage IIA, IIB, or IIIA breast carcinoma who had , 10 positive lymph nodes and who were participants in Cancer and Leukemia Group B (CALGB) 9082 were enrolled in this companion study, CALGB 9066. Patients were randomized to receive either high-dose cyclophosphamide, carmustine, and cisplatin (CPA/cDDP/BCNU) and autologous bone marrow transplantation (the HDC arm) or intermediate-dose CPA/cDDP/BCNU as consolidation to adjuvant chemotherapy (the IDC arm). QOL was assessed at baseline and at 3 months, 12 months, 24 months, and 36 months using the Functional Living Index-Cancer (FLIC), the Psychosocial Adjustment to Illness Scale (PAIS)-Self Report, and the McCorkle Symptom Distress Scale (SDS). RESULTS At the 3-month assessment, patients in the HDC arm demonstrated significant worsening of QOL compared with the IDC arm in terms of their physical well being (FLIC, P = 0.023), social functioning (FLIC, P = 0.026; PAIS, P < 0.0001), symptom distress (SDS, P = 0.0002), and total QOL scores (FLIC, P = 0.042). At 12 months, the differences in QOL scores between the HDC arm and the IDC arm had resolved. CONCLUSIONS Patients who received more intensive adjuvant therapy experienced transient declines in QOL. By 12 months after therapy, QOL was comparable between the 2 arms, regardless of therapy intensity, and many QOL areas were improved from baseline. Cancer 2005. © 2005 American Cancer Society. [source]

Long-term follow-up of autologous stem cell transplantation in patients with diffuse mantle cell lymphoma in first disease remission

CANCER, Issue 12 2003
2 -microglobulin, The prognostic value of, the tumor score
Abstract BACKGROUND The current study was conducted to analyze the long-term results of autologous stem cell transplantation (ASCT) in patients with diffuse mantle cell lymphoma (MCL) in first disease remission. METHODS Thirty-three patients were treated. Thirty-one patients had Ann Arbor Stage III or Stage IV disease. The hyper-CVAD regimen (hyperfractionated intense-dose cyclophosphamide, vincristine, continuous intravenous infusion of doxorubicin, and dexamethasone, alternating with high doses of cytarabine and methotrexate plus leucovorin rescue) was used for cytoreduction before ASCT. Patients were consolidated with high-dose cyclophosphamide (120 mg/kg), total body irradiation, and ASCT. RESULTS At a median follow-up of 49 months, the overall survival and disease-free-survival rates at 5 years were estimated to be 77% and 43%, respectively. Patients whose M. D. Anderson Lymphoma Tumor Score (TS) was , 1 at the time of diagnosis or transplantation experienced longer disease-free survival compared with those whose TS was > 1 (P = 0.02). A ,2 -microglobulin (,2m)level , 3 mg/L at the time of diagnosis or transplantation was also found to be strongly predictive of longer survival (5-year survival rate of 100% vs. 22% in patients with a ,2m level > 3 mg/L) (P = 0.0001). CONCLUSIONS ASCT may prolong the overall survival in a subset of patients with MCL. This improvement has been observed for the most part in patients with low ,2m levels (, 3 mg/L) and TS (, 1). Randomized trials are required to fully assess the benefits of this strategy. Cancer 2003;98:2630,5. © 2003 American Cancer Society. [source]

Late potentials and QT dispersion after high-dose chemotherapy in patients with non-Hodgkin lymphoma

CLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 3 2010
Taru Kuittinen
Summary The most common cardiotoxic effects of high-dose cyclophosphamide (CY) are electrocardiographic changes and transient arrhythmias. Therefore, we prospectively assessed serial electrocardiogram (ECG) and signal-averaged electrocardiogram (SAECG) recordings in 30 adult patients with non-Hodgkin lymphoma (NHL) receiving high-dose CY as part of high-dose chemotherapy (HDT) regimen. All patients were treated with anthracyclines earlier. Heart-rate-corrected QT interval and QT dispersion (QTc and QTc dispersion) were measured from ECG. QRS duration and late potentials (LPs) were analysed from SAECG. Both ECG and SAECG were recorded 1 day (d) prior to HDT (d,7) at baseline, and 1 day (d,2), 7 days (d+7), 12 days (+12) and 3 months (m+3) after HDT. Stem cells were infused on day 0 (d0). Cardiac systolic and diastolic function were assessed on (d,7), (d+12) and (m+3) by radionuclide ventriculography. At baseline, four patients presented with LPs. Cardiac systolic function decreased significantly (53 ± 2; 49 ± 2%, P = 0·009 versus baseline), whilst no patient developed acute heart failure. QRS duration prolonged and RMS40 reduced significantly versus baseline (104 ± 3; 107 ± 3 ms, P = 0·003; 41 ± 4; 38 ± 3 ,V, P = 0·03), and six patients (21%) presented with LPs after CY treatment. Both QTc interval and QTc dispersion increased versus baseline (402 ± 5; 423 ± 5 ms, P<0·001; 32 ± 2; 44 ± 3 ms, P = 0·012), and six patients (20%) developed abnormal QT dispersion. In conclusion, high-dose CY causes subclinical and transient electrical instability reflected by occurrence of LPs as well as increased QTc interval and QT dispersion. Thus, longer follow-up is required to confirm the meaning of these adverse effects on cardiac function and quality of life. [source]

Liver transplantation for sinusoidal obstructive syndrome (veno-occlusive disease): case report with review of the literature and the UNOS database

CLINICAL TRANSPLANTATION, Issue 4 2008
Fernando E. Membreno
Abstract:,Background:, Severe sinusoidal obstructive syndrome (SOS) is a life-threatening complication of stem cell transplantation. We report the case of a young man transplanted for SOS. Method:, A single chart review with query of the United Network of Organ Sharing database and review of the medical literature. Case:, A 23-yr-old male diagnosed with chronic myeloid leukemia underwent a matched unrelated stem cell transplant. The conditioning regimen included high-dose cyclophosphamide and busulfan. Within one month, he developed painful hepatomegaly, jaundice, ascites, and weight gain, and was diagnosed with biopsy-proven SOS. Despite therapy with defibrotide, he continued to deteriorate with the development of progressive renal failure and encephalopathy. The patient underwent orthotopic liver transplantation. After surgery, he developed cytomegalovirus infection and six wk later presented with a bile leak, hepatic artery thrombosis, and a liver abscess. A repeat bone marrow biopsy showed no evidence of recurrent disease. Although the patient was listed for re-transplantation, he succumbed prior to an organ becoming available. Conclusion:, Severe SOS in the setting of bone marrow transplantation portends a poor prognosis. Careful patient selection, timing, and perhaps less immunosuppression should be considered when performing a liver transplantation in the setting of severe SOS. [source]