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Biomedical subjects

Y Nieto

Publications and source records attributed to Y Nieto.

34 records · Page 2Linked to original sources
PubMed1999

Post-mortem incidental finding of cytomegalovirus oophoritis after an allogeneic stem cell transplant.

Cytomegalovirus (CMV) disease is a common and serious complication of allogeneic stem cell transplantation (SCT). Its two most frequent manifestations are interstitial pneumonitis and gastroenteritis. We describe here the first reported case of CMV ovarian infection in an allo-SCT recipient. This patient was included in a clinical trial of high-dose chemotherapy (HDCT) with HLA-matched peripheral SCT for metastatic breast cancer. She expired 53 days after transplantation from organ failure unrelated to her CMV oophoritis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

High-dose therapy with autologous hematopoietic cell support as salvage treatment for patients with breast cancer who have relapsed after previous high-dose chemotherapy.

Twenty-six patients with breast cancer who had relapsed after previously receiving high-dose chemotherapy and autologous hematopoietic cell support received a second course of high-dose cytoreductive therapy and autologous hematopoietic cell support as salvage therapy. Several different high-dose therapy regimens were employed for the second transplant, including a radiolabeled immunoconjugate. Two patients died of treatment-related complications. The remaining 24 patients relapsed a median of 126 (range 22-635) days after salvage transplant. All have since died. The median survival after salvage transplant was 362 (range 31-931) days. We conclude that second courses of high-dose therapy as salvage treatment are generally well-tolerated but their efficacy is modest. Alternative treatment strategies are needed for these patients.

Adult↗
PubMed1999

Acute encephalopathy: a new toxicity associated with high-dose paclitaxel.

The purpose of this study was to describe acute encephalopathy as a new toxicity associated with paclitaxel, when it is delivered at high doses (> or =600 mg/m2) with stem cell support. A total of 129 patients, included in clinical trials of paclitaxel-containing high-dose chemotherapy, were analyzed. A total of 114 patients received paclitaxel at a dose of > or =600 mg/m2. Six patients presented acute encephalopathy starting between 7 and 23 days after paclitaxel treatment; two of them had received prior whole-brain irradiation. Paclitaxel was given alone (one patient), with cyclophosphamide and cisplatin (two patients), and with cyclophosphamide and cisplatin plus 1,3-bis(2-chloroethyl)-1-nitrosourea (three patients). Central nervous system toxicity consisted of rapid obtundation and coma (five patients) and severe confusional picture with paranoid ideations (one patient). Brain magnetic resonance imaging showed diffuse white matter atrophy (one patient) or multiple small infarcts (one patient), or it was normal (four patients). Other complementary tests, including cerebrospinal fluid analysis and electroencephalography, were nondiagnostic. An effect from concomitant psychotropic medications or from other organ toxicities was excluded in all patients. Three patients recovered after 8-15 days, either spontaneously (two patients) or after high-dose steroids (one patient). Three patients died of irreversible coma. Necropsy, performed in two patients, showed generalized white matter atrophy and multiple brain parenchymal infarcts, respectively. No pharmacodynamic correlation between the occurrence of encephalopathy and a pharmacokinetic parameter of paclitaxel could be identified. Paclitaxel-containing high-dose chemotherapy can cause severe acute encephalopathy. An aggravating effect from prior brain irradiation or concurrent 1,3-bis(2-chloroethyl)-1-nitrosourea seems possible.

Antineoplastic Agents, Alkylating↗
PubMed1999

Nonpredictable pharmacokinetic behavior of high-dose cyclophosphamide in combination with cisplatin and 1,3-bis(2-chloroethyl)-1-nitrosourea.

Our objective was to assess whether the total area under the curve (AUC) of high-dose cyclophosphamide (CPA), combined with cisplatin and 1,3-bis(2-chloroethyl)-1-nitrosourea, could be predicted from its AUC on the first day of treatment. We reviewed the AUC of CPA in 470 patients who underwent pharmacokinetic monitoring of the drug. All patients received the same high-dose regimen of CPA, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea (STAMP-I) with identical antiemetic support. Subsequently, patients who experienced a toxic death, relapsed after high-dose chemotherapy, or remained relapse-free at a minimum follow-up of 1 year after high-dose chemotherapy were analyzed for a correlation between the total AUC of CPA and both relapse-free survival and toxic death. The AUC of CPA decreased from day 1 to day 2 in most patients. However, its changes from day 2 to day 3 varied significantly. Neither the value of AUC on day 1 nor its decreasing trend from day 2 to day 3 could predict the AUC on day 3 and the total AUC. Our pharmacodynamic analysis in 335 patients failed to show a correlation between the total AUC of CPA and either toxic death or relapse-free survival. The significant intersubject variability in the AUC of CPA makes the final AUC of the drug unpredictable from an initial measurement on day 1. Thus, in this combination, measurement of levels of parent CPA, with the objective of real-time therapeutic monitoring of this drug, is not informative.

Analysis of Variance↗
PubMed1999

Phase II trial of high-dose chemotherapy with autologous stem cell transplant for stage IV breast cancer with minimal metastatic disease.

The purpose of this study was to assess the efficacy of high-dose chemotherapy (HDC) with autologous stem cell transplant in stage IV breast cancer patients with minimal metastases. Eligible patients had (a) disease that could be resected en bloc and/or irradiated with curative intent using a single field and could, thus, be rendered as having no evidence of disease (NED); and/or (b) <5% bone marrow involvement. From September 1991 to August 1997, 40 consecutive patients were prospectively entered on the study. Pre-HDC local treatment consisted of surgery (n = 31) and radiotherapy (XRT; n = 3). All patients received HDC with cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea and autologous stem cell transplant, with or without CD34 selection. Following HDC, 22 patients received XRT. Four patients died of treatment-related complications. Eighteen patients developed grade 3 nonhematological toxicities (15 lung, 2 cardiomyopathy, and 1 optic neuritis), which resolved with therapy. Within a median follow-up of 49 (15-91) months, 14 patients had relapsed. Twenty-five patients (62.5%) were alive, and 22 patients (55%) were alive and free of disease. Median event-free and overall survivals were 43 and 77 months, respectively. In the subset of patients with one metastatic site, 17 of 24 (68%) remained relapse free. Grade 2 tumors, a single metastatic site, and delivery of XRT were favorable predictors of relapse-free survival in univariate but not multivariate analyses. Inclusion of HDC, as described, in the multimodal treatment of stage IV breast cancer patients with minimal metastases is promising. These results warrant prospective randomized trials with a HDC-containing arm in this patient population.

Adult↗
PubMed1999

A predictive model for relapse in high-risk primary breast cancer patients treated with high-dose chemotherapy and autologous stem-cell transplant.

High-dose chemotherapy (HDCT) is currently under evaluation for high-risk primary breast cancer (HRPBC), defined by extensive axillary nodal involvement or inflammatory breast carcinoma. Phase II studies of HDCT for HRPBC show that 30-40% of patients eventually relapse. We retrospectively reviewed 176 patients enrolled in clinical trials of HDCT for HRPBC at the University of Colorado and analyzed 23 potential predictive variables for relapse. All of the patients received the same regimen, with cyclophosphamide, cisplatin, and BCNU. Nine patients who experienced a toxic death were excluded from this analysis. The resulting predictive model was subsequently tested in an independent patient set treated at Duke University with the same HDCT regimen. Nodal ratio (number of involved nodes:number of sampled nodes), tumor size, grade, stage, estrogen receptor, progesterone receptor, and clinical inflammatory breast carcinoma correlated with risk of relapse. Nodal ratio, tumor size, and the combined estrogen receptor/progesterone receptor status were independent predictors. A scoring system using those three variables determines the risk of relapse, with a sensitivity and specificity of 60 and 90%, respectively, and a positive and negative predictive value of 65 and 88%, respectively. The differences in relapse-free survival and overall survival between high- and low-score patients were highly significant (P<0.000001). This model was subsequently validated in the Duke patient set. This model can identify two subgroups of HRPBC patients with low (12%) and high (65%) risk for recurrence after HDCT. Future research that tests new therapies will focus on those patients with a high score.

Adult↗
PubMed1998

Weekly continuous infusion of 5-fluorouracil with oral leucovorin in metastatic breast cancer patients with primary resistance to doxorubicin.

Doxorubicin-resistant metastatic breast cancer (MBC) is a very poor prognosis scenario, where only taxanes have shown activity, often at the expense of severe toxicity that compromises palliation. This study was undertaken to test the antitumor activity and tolerability of infusional 5-fluorouracil (5-FU) modulated with low-dose oral leucovorin (LV), in heavily pretreated patients with stringent criteria of primary resistance to doxorubicin, visceral involvement, and suboptimal performance status. Twenty-six patients with measurable MBC and primary resistance to anthracyclines received a weekly outpatient 48-hour infusion of high-dose 5-FU with low dose oral leucovorin. All patients were assessable for response and toxicity. Eight partial responses were seen (30% response rate) in soft tissue and visceral sites, with a median response duration of eight months (5 + to 12). 98% of the cycles were minimally toxic or non-toxic. Toxicities included mucositis, diarrhea, and plantar-palmar-syndrome. Our results suggest that this schedule of LV-modulated infusional 5-FU can produce a substantial number of long-lasting responses and meaningful palliation to this very poor prognosis population.

Administration, Oral↗
PubMed1998

High-dose chemotherapy with autologous hematopoietic progenitor-cell support as part of combined modality therapy in patients with inflammatory breast cancer.

PURPOSE: To evaluate the feasibility of high-dose chemotherapy (HDC) with autologous hematopoietic progenitor-cell support (AHPCS) as part of combined modality therapy (CMT) in patients with inflammatory breast cancer (IBC). PATIENTS AND METHODS: From April 1993 to March 1997, 30 patients with IBC were treated at our program. Twenty-three patients received neoadjuvant chemotherapy (NAC) before HDC; 18 patients also received adjuvant chemotherapy following surgery, but before HDC. All patients received HDC with high-dose cyclophosphamide, cisplatin, and carmustine (BCNU) with AHPCS. Every patient underwent surgery either before (27 patients) or after (three patients) HDC. Patients received radiotherapy after HDC in addition to tamoxifen if their tumors were estrogen receptor-positive. RESULTS: Thirteen patients experienced grade 3 or 4 nonhematologic noninfectious toxicities. In 12 patients (40%), this represented drug-induced lung injury, which in all cases responded to a 10-week course of corticosteroids. The only treatment-related death was secondary to hemolytic-uremic syndrome (HUS). Another patient suffered grade 4 CNS toxicity, which was completely reversible. All patients engrafted promptly. Eight patients relapsed, five of whom had a poor pathologic response to NAC. Relapses were local (five patients), local plus systemic (one), or systemic only (two). Median follow-up time from diagnosis and HDC is 23.5 (range, 7 to 49) and 19 (range, 4 to 44) months, respectively. Twenty-one patients (70%; 95% confidence interval [CI], 51% to 86%) remain alive and free of disease 4 to 44 months after HDC. Median disease-free survival (DFS) and overall survival have not yet been reached. CONCLUSION: HDC as part of CMT is feasible in patients with IBC. The toxicity of this treatment program is significant, but tolerable. Despite the short follow-up duration, the promising DFS observed in this group of patients warrants randomized studies that include a HDC-containing arm in patients with IBC.

Adenocarcinoma↗
PubMed1997

[High-dose chemotherapy with four drugs and peripheral blood progenitor cell autologous transplantation in disseminated breast cancer].

OBJECTIVE: To evaluate the therapeutic efficacy (in terms of overall survival [OS] and progression-free survival [PFS]) of a high-dose chemotherapy protocol including four drugs and peripheral stem cell rescue (PSCR) plus posttransplant G-CSF (filgrastim) in disseminated breast cancer patients. PATIENTS AND METHODS: Fifty-three metastatic breast cancer patients were treated with a four-drug program of high-dose chemotherapy including cyclophosphamide (6 g/m2), thiotepa (500 mg/m2), carboplatin (800-1,600 mg/m2) and mitoxantrone (20-60 mg/m2) with autologous peripheral blood progenitor cell support followed by filgrastim. Most cases (92%) had previously received conventional induction chemotherapy with anthracycline-containing combinations. RESULTS: After a median follow-up of 27 months (range 12-43 months) from transplant, the median survival of the overall group was 25 months, with an OS projected at 43 months of 31%. Patients in complete remission after induction chemotherapy or status NED (no evidence of disease: surgical resection of metastases) presented the best outcome, with a projected PFS of 50% at 43 months. Patients intensified without complete response had a poor outcome. The most important extramedullary toxicity was mucositis. Four patients (7.5%) died as a consequence of treatment (2 with sepsis-associated ARDS, one with venooclussive disease of the liver, one with congestive cardiac failure). CONCLUSIONS: The outcome of metastatic breast cancer patients in complete remission after induction chemotherapy or NED status seems to be good with our high-dose chemotherapy including four drug and PSCR. On the other hand, patients intensified without complete response presented a bad outcome and do not seem candidates for future trials with this therapeutic approach.

Adult↗
PubMed1997

Preliminary results. UFT/methotrexate/leucovorin for breast Ca patients in progression after HDCT/PBPC support.

Twenty-four patients with metastatic breast cancer that had progressed after high-dose chemotherapy with peripheral blood progenitor cell (PBPC) support were given intramuscular methotrexate in combination with oral UFT (tegafur and uracil) and oral leucovorin (the MUL regimen). Of the total treated, 21 patients are currently evaluable for response and toxicity. All patients had received extensive prior chemotherapy, including a high-dose regimen with PBPC support. Of the 21 assessable patients, 8 obtained either a complete response (1) or partial response (7), for an overall objective response rate of 38%. Another 7 patients had stable disease for 3 or more months. Therefore, the MUL regimen was able to stop disease progression for 3 or more months in nearly 75% of patients. The median time to progression and median overall survival from the start of MUL were 6 and 9 months, respectively. The toxicity was mainly gastrointestinal; 6 patients (29%) had World Health Organization grade 2/3 diarrhea, leading to a UFT dose reduction. Emesis was mild and easily manageable with thiethylperazine. In conclusion, MUL chemotherapy is active and well tolerated in patients with metastatic breast cancer in progression after high-dose chemotherapy. Further studies with this regimen, either as salvage chemotherapy or as maintenance chemotherapy after high-dose chemotherapy with PBPC, are warranted.

Adult↗
PubMedDate not supplied

Peripheral blood stem cell transplantation in breast cancer.

Over the past decade, peripheral blood progenitor cells (PBPCs) have replaced bone marrow as the major source of haematopoietic support. This transition from marrow to PBPCs is due to the fact that, for many clinical studies, a significantly faster rate of engraftment, particularly for platelets, has been demonstrated for patients who receive PBPC support when compared to similarly treated patients who are transplanted with bone marrow. The leukapheresis procedure itself, quality of PBPC graft, methods of PBPC mobilization, purging, and ex vivo expansion will be discussed in detail.

Breast Neoplasms↗