Blood Stem Cell Support Research Articles

Breast cancer cell contamination of blood stem cell products in patients with metastatic breast cancer: predictors and clinical relevance.

The incidence and clinical relevance of tumor cells contaminating the stem cell products of patients with advanced breast cancer treated with high-dose chemotherapy is uncertain because prior studies used small sample sizes and lacked standardization of the immunocytochemistry (ICC) detection method used. We evaluated blood stem cell and bone marrow samples obtained from 535 women with metastatic breast cancer who received high-dose chemotherapy and unmanipulated mobilized blood stem cell support. Of the patients tested, 20.6% and 26.3% had blood stem cell and bone marrow contamination, respectively. Blood stem cell contamination was significantly more frequent in patients with marrow involvement than in patients without marrow involvement (35% versus 18.4%, respectively; P = .009). In fact, according to multivariate analysis results, marrow involvement was the only significant predictor for blood stem cell product contamination. Patients without marrow involvement who had fewer apheresis procedures were also observed to have a significantly lower incidence rate of blood stem cell contamination than patients who had more procedures (P < or = .008), and patients who received combined chemotherapy and cytokine mobilization therapy had less contamination than patients who received cytokine alone (P = .0001). Combined mobilization therapy appears to be associated with a lower incidence of contamination as a result of fewer apheresis procedures rather than through an antitumor effect of chemotherapy (P < or = .001). Patients with ICC-negative blood stem cell products had significantly longer progression-free survival (PFS) and overall survival (OS) than did patients with ICC-positive blood stem cell products (median PFS, 401 versus 291 days, respectively, P = .007; median OS, 1060 versus 697 days, P = .009) . However, multivariate analysis did not reveal any significant independent predictors of survival outcomes. Thus, further study is needed to determine if contaminating tumor cells in the stem cell products of breast cancer patients ever directly impact survival outcomes or are only indicative of residual in vivo disease in high-dose chemotherapy recipients.

Peripheral blood stem cell support reduces the toxicity of intensive chemotherapy for children and adolescents with metastatic sarcomas.

To increase the dose intensity (DI) of chemotherapy for pediatric patients with metastatic sarcomas, including the Ewing sarcoma family of tumors (ESFT) and rhabdomyosarcoma (RMS), the authors tested the feasibility of an intensive regimen supported by granulocyte-colony stimulating factor (G-CSF) and peripheral blood stem cells (PBSC). Twenty-three children and adolescents with metastatic sarcomas received vincristine, doxorubicin, cyclophosphamide, ifosfamide, sodium mercaptoethanesulfonate (mensa), and etoposide (VACIME) chemotherapy, consisting of 8 courses of vincristine 2 mg/m(2) on Day 0, doxorubicin 37.5 mg/m(2) per day on Days 0-1, cyclophosphamide 360 mg/m(2) per day on Days 0-4, ifosfamide 1800 mg/m(2) per day on Days 0-4, mesna 2400 mg/m(2) per day, and etoposide 100 mg/m(2) per day on Days 0-4. Doxorubicin was omitted in Courses 7 and 8. G-CSF was given after each course of therapy. Courses of therapy were repeated every 21 days or as soon as hematopoietic recovery permitted. PBSC were collected twice: first, after Course 2 (infused after Courses 3 and 4) and, second, after Course 4 (infused after Courses 5 and 6). Surgical resection followed Course 6, and radiotherapy followed Course 8. PBSC collections were adequate in 91% of all harvests. The mean DI was 82% (standard deviation, 14%) of the intended DI, which was greater than historic data without PBSC support. Seventeen patients (74%) achieved a complete response (CR), 12 patients with chemotherapy alone and 5 more patients after undergoing surgical resection. Fifteen patients developed progressive disease, with a 2-year event free survival (EFS) rate of 39% (95% confidence interval, 19-59%). Hematopoietic toxicity was severe and cumulative, although it was less than that seen previously without PBSC support. PBSC-supported multicycle chemotherapy is a feasible method to increase chemotherapy DI for pediatric patients with metastatic sarcomas. Although the CR rate compared favorably with previously reported response rates, the 2-year EFS rate was similar to that achieved with other intensive regimens.

566 Poster Encouraging early results of a phase 1/2 trial of high activity rhenium-186 HEDP with autologous peripheral blood stem cell support in progressive hormone refractory prostate cancer metastatic to bone

566 Poster Encouraging early results of a phase 1/2 trial of high activity rhenium-186 HEDP with autologous peripheral blood stem cell support in progressive hormone refractory prostate cancer metastatic to bone

Radiotherapy after high-dose chemotherapy and peripheral blood stem cell support in high-risk breast cancer

Purpose: To assess the toxicity and efficacy of radiotherapy with respect to locoregional control after adjuvant high-dose chemotherapy for patients with breast cancer. At first, radiotherapy was withheld because of toxicity concerns, but it was introduced in 1995 because of reported high locoregional relapse rates. Methods and Materials: Between 1992 and 1998, 40 patients with Stage II–III high-risk breast cancer received adjuvant high-dose chemotherapy consisting of thiotepa, mitoxantrone, and cyclophosphamide and peripheral blood stem cell support after four cycles of induction chemotherapy. The chest wall or breast, as well as the supraclavicular nodes, were irradiated with electrons and photons to a median dose of 50.4 Gy in 20 patients. Six additional patients received only supraclavicular irradiation to a median dose of 50.4 Gy. Acute toxicity was scored clinically. Pulmonary function tests were performed in 14 irradiated patients before high-dose chemotherapy and 1.1–4.4 years (median 1.6) after irradiation. The median follow-up time of living patients was 33 vs. 67 months in irradiated ( n = 26) and nonirradiated ( n = 14) patients, respectively. Results: G2 and G3 hematologic toxicity occurred in 1 patient each. No clinical pneumonitis or clinical impairment of lung function was observed. After 1–2 years, the lung function tests showed only minor changes in 4 patients. The 3-year locoregional control rate was 92% in the irradiated patients vs. 58% in the nonirradiated patients ( p = 0.049, actuarial analysis). Conclusion: In this series, adjuvant radiotherapy after adjuvant chemotherapy for breast cancer appeared well tolerated, with improved local regional control and without significant side effects. Longer follow-up and more patient accrual, as well as Phase III trials, are necessary for confirmation.

Population pharmacokinetic and limited sampling models for carboplatin administered in high-dose combination regimens with peripheral blood stem cell support.

By means of a nonlinear mixed effect modeling technique, a population pharmacokinetic (PK) model was developed to evaluate the effects of a variety of covariates on clearance and other pharmacokinetic parameters of ultrafilterable carboplatin administered in high-dose combination regimens with peripheral blood stem cell support. In addition, single-sample and two-sample limited sampling models (LSMs) were derived to estimate carboplatin's AUC that could be used in the design of drug dosing regimens. A total of 44 female patients with advanced ovarian cancer participated in two phase I studies. All 44 patients received a high-dose carboplatin chemotherapy with other anticancer drugs. A population PK model was applied to the plasma concentration-time data of ultrafilterable carboplatin using the NONMEM and Xpose computer programs. The Xpose program utilized a general additive modeling technique to identify significant patient covariates and PK parameter relationships. The resultant PK model was validated using a bootstrap method. Stepwise linear regression analyses were used to develop LSMs based on the correlation between carboplatin's AUC and plasma concentrations. The best structural covariate-free model for high-dose carboplatin was a linear two-compartment model with an exponential error model to account for intersubject variability and a CCV error model to account for intrasubject variability. Subsequently, a final covariate model for clearance (l/min) was obtained as follows: TVCL=0.101+0011*(WT-62.35)-0.0658*(SCR-0.65) where WT is body weight (kg) and SCR is serum creatinine (mg/dl). Both WT and SCR were found to significantly influence carboplatin's total clearance. It was determined that the best single-sample LSM was AUC(LSM)=0.553*C(240min) ( r=0.998). Both a population PK model and a LSM for high-dose carboplatin were developed following its administration in combination chemotherapeutic regimens with peripheral blood stem cell support. In both cases, the models performed well when analyzed in the context of the retrospective and bootstrap analyses. Prospective studies in ovarian cancer patients should be conducted to further tailor the current models.

High dose chemotherapy and stem cell support for poor risk and recurrent nonseminomatous germ cell cancer: initial experience with sequential therapy

Approximately 20% of patients with germ cell tumours do not respond fully to standard therapy, or relapse after treatment. The prognosis of these patients is poor with conventional chemotherapy. Preliminary data suggest that they may have a higher durable response rate with high dose chemotherapy and peripheral blood stem cell support. To treat a group of testicular cancer patients, either with relapsed disease or with poor prognostic features initially, with high dose chemotherapy and stem cell support, and evaluate their outcome. Five patients with testicular cancer were treated with high dose chemotherapy and stem cell support. Of these, four underwent this treatment as salvage therapy and one patient with poor prognostic features was treated as primary treatment. At an average follow-up of 18 months, four patients remain free of disease while one patient has developed relapse. This report provides further support for high dose chemotherapy in this setting although randomised, controlled trials are essential to clarify its use.

P53 is the strongest predictor of survival in high-risk primary breast cancer patients undergoing high-dose chemotherapy with autologous blood stem cell support.

Our purpose was to determine the predictive value of tumor biologic parameters in patients with HRPBC who received HDCT with ASCT as first-line treatment. From September 1992 to May 2000, 149 stage II or III HRPBC patients were enrolled in a single-arm trial using a tandem HDCT regimen followed by ASCT. Her2/neu, p53, Ki67 and bcl-2 protein expression was studied using immunohistochemic staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA index) and tumor cell proliferation (SPF) were measured by DNA flow cytometry. The relationship between these tumor biologic parameters, on the one hand, and DFS, DDFS and OS, on the other, was analyzed. With a median follow-up of 43 months (range 7-106), p53 protein accumulation (p = 0.000004), negative combined hormone receptor status (p = 0.003) and Her2/neu overexpression (p = 0.02) were significant negative predictors of OS in univariate analysis. A poorer DFS was associated with p53 positivity (p = 0.04) and nodal ratio > or = 0.8 (p = 0.008). Poorer DDFS was associated with p53 positivity (p = 0.03). In multivariate analysis, Her2/neu overexpression (RR = 3.86, 95% CI 1.48-10.1, p = 0.006) and p53 overexpression (RR = 6.06, 95% CI 2.22-16.52, p < 0.001) proved to be independent predictors of adverse OS. p53 overexpression was the only independent predictor of DFS (RR = 2.21, 95% CI 1.07-4.57, p = 0.03). p53 overexpression and Her2/neu overexpression are independent negative predictors of survival in HRPBC treated with HDCT. The adverse impact of these biologic features was probably not altered by HDCT. For HRPBC patients with tumors not overexpressing Her2/neu or p53, HDCT may be an appropriate approach to achieve long-term survival and tumor control.

Newly diagnosed multiple myeloma.

Melphalan combined with prednisone (MP) has been accepted as the standard therapy for previously untreated multiple myeloma (MM) because most studies demonstrate only a modest survival benefit of combination chemotherapy regimens when compared with MP. There have been modest gains with more intensive myeloablative regimens in combination with blood stem cell support, particularly for patients with early primary refractory disease who subsequently achieve partial remission, and for the approximately 25% to 35% of patients achieving complete remission. To preserve the ability to adequately collect stem cells, the use of alkylating agents, such as melphalan, should be limited in the previously untreated patient with myeloma (including those older than 65 years of age) who is a candidate for myeloablative therapy. Pulse dexamethasone-containing regimens provide rapid responses and may be considered the first regimens of choice. Although vincristine/doxorubicin/dexamethasone (VAD) produces responses in approximately 50% to 70% of patients with previously untreated multiple myeloma, use early in the disease has not improved survival. Outside of a specific study protocol, this regimen may be best reserved for patients with refractory (particularly relapsing) disease. Notable exceptions include patients with renal failure or plasma cell leukemia in whom the rapid responses provided by VAD may avoid potentially permanent, serious complications. Recently, new agents with novel mechanisms of action (ie, thalidomide, immunomodulatory drugs, proteosome inhibitors) have demonstrated activity in resistant myeloma. Because these agents are likely to show activity alone or in combination, newly diagnosed patients and previously untreated patients should be considered for clinical trials. Thalidomide/dexamethasone has already produced response rates of 65% to 75% in previously untreated patients. Its ease of administration along with stem cell preservation are likely to make this, followed by myeloablative therapy with stem cell support, the treatment of choice for untreated myeloma as confirmatory studies are completed.

High-dose chemotherapy in breast cancer: Where are we now?

High-dose chemotherapy (HDCT) with peripheral blood stem cell support is often used in high-risk patients with breast cancer. Most investigators performing these procedures provide anecdotal experience that complete remissions occur more commonly with HDCT than standard therapy. However, prospective studies have not convincingly demonstrated an advantage of HDCT in either the adjuvant or metastatic disease setting. The emergence of newer agents, such as the taxanes and trastuzumab, and their incorporation into treatment regimens may create a new standard against which HDCT must be evaluated. In addition, the heterogeneity of breast cancer patients represents an important barrier that must be addressed in future evaluations of HDCT. New prospective, randomized, clinical trials of HDCT are needed, which will incorporate the newer anticancer agents in standard therapy and enroll patients according to multiple well-defined risk factors. Until these studies are conducted, many questions will remain unanswered concerning the role of HDCT in breast cancer. Given its encouraging results in other malignancies, there is ample evidence to continue evaluating HDCT in controlled clinical trials. Semin Oncol 29 (suppl 8):16-20. Copyright 2002, Elsevier Science (USA). All rights reserved.

High-dose chemotherapy in breast cancer: where are we now?

High-dose chemotherapy (HDCT) with peripheral blood stem cell support is often used in high-risk patients with breast cancer. Most investigators performing these procedures provide anecdotal experience that complete remissions occur more commonly with HDCT than standard therapy. However, prospective studies have not convincingly demonstrated an advantage of HDCT in either the adjuvant or metastatic disease setting. The emergence of newer agents, such as the taxanes and trastuzumab, and their incorporation into treatment regimens may create a new standard against which HDCT must be evaluated. In addition, the heterogeneity of breast cancer patients represents an important barrier that must be addressed in future evaluations of HDCT. New prospective, randomized, clinical trials of HDCT are needed, which will incorporate the newer anticancer agents in standard therapy and enroll patients according to multiple well-defined risk factors. Until these studies are conducted, many questions will remain unanswered concerning the role of HDCT in breast cancer. Given its encouraging results in other malignancies, there is ample evidence to continue evaluating HDCT in controlled clinical trials.

Intensive chemotherapy with whole blood stem-cell support and concurrent chest radiotherapy in small cell lung cancer: a phase I/II trial

Intensive chemotherapy combined with chest radiation may ameliorate survival in small cell lung cancer (SCLC). In a prospective study, we treated 18 patients with limited SCLC with an intensive sequential single agent (ifosfamide, carboplatin, etoposide and paclitaxel, (ICE-T)) chemotherapy with the support of unprocessed stem-cell enriched whole blood and G-CSF and concomitant bi-fractionated chest radiotherapy (60 Gy). The treatment was delivered in a short time of 10 weeks. The results were compared with an historical patient group treated with six cycles of standard chemotherapy of etoposide and cisplatin and concomitant chest radiotherapy. After a 3-year median follow up, the 2-year progression free (PFS) and overall survival (OS) are 54 and 63% in the ICE-T group, respectively. In the control group, median PFS and OS were 13 and 17 months and the 2-year PFS and OS were 32% ( P=0.20) and 47% ( P=0.25), respectively. This short and intensive chemo-radiotherapy regimen is well tolerated and induces promising survival results. The use of stem cell enriched whole blood should be investigated in larger randomized studies.

Hematopoietic stem cell transplantation in the treatment of multiple myeloma

Multiple myeloma is a malignant clonal plasma cell disorder that accounts for about 10% of all hematological malignancies. Conventional melphalan-based chemotherapy produces less than 5% of complete remission rates, with less than 5% of patients surviving 10 years or more. The VAD regimen is very effective to induce cytoreduction, but does not prolong event free survival or overall survival. High-dose therapy with autologous bone marrow or peripheral blood stem cell support induces complete remission in 30%-50% of patients, with a very low transplant related mortality (<5%). Both event free survival and overall survival are prolonged with High-dose therapy, but relapses continue to be a major problem. A subset of patients (chromosome 13 abnormalities and high level of beta2-microglobulin at diagnosis) at high risk of relapse has been identified. Double transplants and post-transplant strategies, with the use of alpha interferon, thalidomide, or combined chemotherapy, are additional measures used to reduce the incidence of relapse. Allogeneic transplants can induce durable molecular remissions. However, the very high (30%-50%) transplant-related mortality limits the application of this procedure. The emerging concept of non-myeloablative transplants may be a very attractive alternative to improve these results. This strategy may be associated with lower transplant related mortality, and yet provide a graft versus myeloma effect, potentially increasing event free survival and overall survival.

Stem cell dose and tumorbiologic parameters as prognostic markers for patients with metastatic breast cancer undergoing high-dose chemotherapy with autologous blood stem cell support.

We report on the prognostic significance of tumorbiologic parameters and CD34(+) cell dose in 120 patients with metastatic breast cancer (MBC) who received high-dose chemotherapy (HDCT) with autologous blood stem cell transplantation as first-line treatment. Her2/neu, p53, Ki67, and bcl-2 protein expression were studied using immunohistochemical staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA-index) and tumor cell proliferation (S-phase fraction) were measured by DNA flow cytometry. The relationship between these parameters and the CD34(+) cell dose and progression free (PFS) and overall survival (OS) was analyzed. With a median follow-up period of 40 months (range, 7-89 months), no more than two metastatic sites (relative risk [RR] = 3.84 [95% confidence interval (CI) 1.49-10]; p =.005) and hyperploidy (RR = 2.58 [95% CI 1.26-5.26]; p =.009) were independent predictors of longer PFS according to multivariate analysis. Independent prognostic factors of longer OS included one or two metastatic sites (RR = 4.16 [95% CI 1.96-4.16]; p <.001), a positive combined hormone receptor status (RR = 2.45 [95% CI 1.45-4.14]; p =.001) and a high number of infused stem cells (>7.8 x 10(6) CD34(+) cells per kg body weight) (RR = 2.0 [95% CI 1.17-3.42]; p =.01). In conclusion, positive hormone receptors, < or =2 metastatic sites, high DNA-index and high CD34(+) cell dose (>7.8 x 10(6) CD34(+) cells per kg) are predictors for a favorable outcome after autotransplantation for MBC. Our observation might indicate a favorable effect of HDCT in MBC patients with overexpression of Her2/neu who might have a worse prognosis when treated with conventional chemotherapy.

High-activity samarium-153-EDTMP therapy followed by autologous peripheral blood stem cell support in unresectable osteosarcoma

Despite highly efficacious chemotherapy, patients with osteosarcomas still have a poor prognosis if adequate surgical control cannot be obtained. These patients may benefit from therapy with radiolabeled phosphonates. Six patients (three male, three female; seven to 41 years) with unresectable primary osteosarcoma (n = 3) or unresectable recurrent sites of osteosarcomas (n = 3) were treated with high-activity of Sm-153-EDTMP (150 MBq/kg BW). In all patients autologous peripheral blood stem cells had been collected before Sm-153-EDTMP therapy. No immediate adverse reactions were observed in the patients. In one patient bone pain increased during the first 48 hrs after therapy. Three patients received pain relief. Autologous peripheral blood stem cell reinfusion was performed on day +12 to +27 in all patients to overcome potentially irreversible damage to the hematopoietic stem cells. In three patient external radiotherapy of the primary tumor site was performed after Sm-153-EDTMP therapy and in two of them polychemotherapy was continued. Thirty-six months later one of these patients is still free of progression. Two further patients are still alive. However, they have developed new metastases. The three patients who had no accompanying external radiotherapy, all died of disease progression five to 20 months after therapy. These preliminary results show that high-dose Sm-153-EDTMP therapy is feasible and warrants further evaluation of efficacy. The combination with external radiation and polychemotherapy seems to be most promising. Although osteosarcoma is believed to be relatively radioresistant, the total focal dose achieved may delay local progression or even achieve permanent local tumor control in patients with surgically inaccessible primary or relapsing tumors.

Feasibility and long-term results of autologous PBSC transplantation in recurrent undifferentiated nasopharyngeal carcinoma.

Recurrent undifferentiated nasopharyngeal carcinoma (UNPC) is a chemosensitive illness. Here we report long-term results of high-dose chemotherapy (HDC) as late intensification, with autologous peripheral blood stem cell (PBSC) support. Six patients (5 men, 1 woman; median age 41years; median ECOG PS = 0) with recurrent UNPC (local, 2; local + nodal, 2; bone metastasis, 2) have been enrolled. All patients had been previously treated with neoadjuvant chemotherapy and radiotherapy; 3 of 4 local relapses had received a re-irradiation. Every patient received three courses of cisplatin + epirubicin and 1 cycle of epirubicin followed by PBSC collection. A median of 7.2 x 10(6)/kg (range, 4.5-18) CD34+ cells were reinfused. HDC was according ICE scheme: ifosfamide, 2.5 g/m(2)/d, + carboplatin, 300 mg/m(2)/d, + VP-16, 300 mg/m(2)/d days 1 through 4. After conventional chemotherapy, we had 1 CR (16%), 3 PR (50%), and 2 NC (34%). After HDC, we had 4 CR (66%),1 PR (17%), and 1 MR (17%). Toxicity was manageable. After a median follow-up of 30 months (range, 14-50), two patients are alive without disease (34%), one is alive with bone disease (16%), and three (50%) died of disease at 16, 18, and 24 months. HDC has an acceptable toxicity, can convert PR in CR, and seems effective, with long-lasting CRs.

High activity rhenium-186 HEDP with peripheral blood stem cell support -a novel approach to hormone refractory prostate cancer metastatic to bone

High activity rhenium-186 HEDP with peripheral blood stem cell support -a novel approach to hormone refractory prostate cancer metastatic to bone

Clinical outcome after front-line intensive sequential chemotherapy (ISC) in patients with aggressive non-Hodgkin’s lymphoma and high-risk international prognostic index (IPI 3): Final analysis of survival in two consecutive ISC trials

Aggressive non-Hodgkin's lymphomas (NHL) in patients under the age of 60 have a very poor prognosis when the international prognostic index (IPI) is high, with an age-adjusted (Aa)-IPI score at 3. In such patients, conventional chemotherapy results in a low complete response (CR) rate of 46%, a five-year survival and disease-free survival (DFS) of 32% and 58%, respectively. For this report we have analyzed whether front-line high-dose chemotherapy could influence the outcome of this group of patients. From 1992 onwards we conducted two pilot clinical trials of intensive sequential chemotherapy (ISC) with growth factors and blood stem cell support as initial treatment in 62 poor-risk patients with aggressive NHL. Of these patients, 33 were considered to be a high-risk group based on the Aa-IPI. The median age was 42 years (range 21-60). The treatment was completed in 88% of patients, 86% receiving greater than 75% or more of the projected dose-intensity. Twenty patients (61%) achieved a CR. At a median follow-up of 48 months (range 26-86), the estimated five-year survival and DFS was 51% (95% confidence interval (CI): 34%-68%) and 70% (95% CI: 50%-90%), respectively. These results suggest that primary treatment using high-dose therapy supported by both growth factors and peripheral blood stem cells can cure up to 50% of high-risk patients with malignant lymphomas.

A randomized trial of high-dose chemotherapy (HDCT) with autologous peripheral blood stem cell support (asct) compared to standard chemo therapy (ct) in women with metastatic breast cancer: a National Cancer Institute of Canada (NCIC) clinical trials group study

A randomized trial of high-dose chemotherapy (HDCT) with autologous peripheral blood stem cell support (asct) compared to standard chemo therapy (ct) in women with metastatic breast cancer: a National Cancer Institute of Canada (NCIC) clinical trials group study

HER-2 expression is a prognostic factor in patients with metastatic breast cancer treated with a combination of high-dose cyclophosphamide, mitoxantrone, paclitaxel and autologous blood stem cell support.

The expression levels of a circulating extracellular domain of HER-2 can be detected in the plasma and serum of patients with metastatic breast cancer using an enzyme immunoassay (ELISA) method. In this study, we evaluated the clinical significance of high and low levels of HER-2 in the plasma of 46 patients with metastatic breast cancer enrolled in a clinical trial of high-dose chemotherapy (HDCT) using cyclophosphamide, mitoxantrone, and paclitaxel with autologous stem cell transplantation (ASCT). Using 2500 U/ml as the cut-point, 20 patients (46%) had elevated HER-2 levels (HER-2 positive). Our results suggest that patients with metastatic breast cancer and high soluble plasma HER-2 have a significantly poorer overall (OS) and progression-free survival (PFS) following high-dose chemotherapy with paclitaxel and ASCT. The median OS of patients with low levels of HER-2 was significantly longer (P < 0.01) than the median OS of patients with high levels of HER-2 (29.8 months vs 15.9 months). PFS was also significantly longer (P < 0.01) for patients who were HER-2-negative, than for patients who were HER-2-positive (13.0 vs 8.6 months). Univariate analysis showed that patients with liver or lung metastases had significantly reduced OS and PFS. Patients with metastases to two or more sites also had a significantly reduced time to disease progression, but not OS. In multivariable analysis, lung metastases contributed along with HER-2-positive status to determine a group of patients with significantly poorer OS. However, HER-2-positive status remained the only independent predictor of PFS.

Autologous Peripheral Blood Stem Cell Transplantation Following Heart Transplantation for Primary Systemic Amyloidosis

A 47 years old woman was admitted with severe congestive heart failure. Cardiac echography showed increased intra-ventricular septum thickness, and there was a serum Ig G LD monoclonal component. Cardiac biopsies confirmed diffuse amyloidosis of Al type. To avoid cardiac toxicity of chemotherapy, the patient received first a heart transplantation (HT), followed six months later by melphaian 200 mg/m2 and autologous peripheral blood stem cell support (PBSCT). This case suggests that such strategy is feasible with a favorable outcome, and HT may be an appropriate procedure for some patients with Al amyloidosis who meet the criteria for PBSCT.