Treating relapsed and refractory metastatic germ cell tumours with high-dose chemotherapy with carboplatin and etoposide and autologous haematopoietic stem cell transplantation.

INTRODUCTION AND AIM: To demonstrate the real-life data about patients who underwent AHSCT due to GCT. METHODS: Between November 2016 and April 2020, 64 patients who received CE as high-dose chemotherapy for AHSCT in the Gulhane Education and Research Hospital were included in the study. Sixty-one patients received one AHSCT with CE chemotherapy regimen. Survival data and clinical characteristics were evaluated retrospectively. RESULTS: The mean age of the patients were 31.9 ± 9 (min-max:18-55). With a median follow-up of 10.7 ± 8.7 months, the 1-year progression-free survival (PFS) rate was 57.8%, and the 1-year overall survival rate was 77.5%. Median overall survival (OS) and progression-free survival (PFS) times were 21.5 ± 1.8 (95% CI: 14.5-33.4) and 20 ± 2 months, respectively. The response rate was 72%. There were three treatment-related deaths. CONCLUSION: This sizeable single-centre study shows that patients with relapsed metastatic GCT are curable by CE as high dose chemotherapy plus AHSCT with reliable toxicity even for a single cycle.

Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutations.

BACKGROUND: Gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) cause susceptibility to a range of infections, autoimmunity, immune dysregulation, and combined immunodeficiency. Disease manifestations can be mild or severe and life-threatening. Hematopoietic stem cell transplantation (HSCT) has been used in some patients with more severe symptoms to treat and cure the disorder. However, the outcome of HSCT for this disorder is not well established. OBJECTIVE: We sought to aggregate the worldwide experience of HSCT in patients with GOF-STAT1 mutations and to assess outcomes, including donor engraftment, overall survival, graft-versus-host disease, and transplant-related complications. METHODS: Data were collected from an international cohort of 15 patients with GOF-STAT1 mutations who had undergone HSCT using a variety of conditioning regimens and donor sources. Retrospective data collection allowed the outcome of transplantation to be assessed. In vitro functional testing was performed to confirm that each of the identified STAT1 variants was in fact a GOF mutation. RESULTS: Primary donor engraftment in this cohort of 15 patients with GOF-STAT1 mutations was 74%, and overall survival was only 40%. Secondary graft failure was common (50%), and posttransplantation event-free survival was poor (10% by 100 days). A subset of patients had hemophagocytic lymphohistiocytosis before transplant, contributing to their poor outcomes. CONCLUSION: Our data indicate that HSCT for patients with GOF-STAT1 mutations is curative but has significant risk of secondary graft failure and death.

An overview of high dose chemotherapy with autologous stem cell rescue for germ cell tumors in current practice.

Testicular cancer is a frequent tumor of adolescent and young adult males. Chemotherapy has been reported to provide cure rates as high as 80% even in the presence of advanced testicular cancer. Studies regarding testicular cancer started after the advent of high dose chemotherapy (HDC) plus atologous stem cell rescue (ASCR) for the treatment of solid tumors in 1980s. Testicular cancer is highly responsive to HDC. Einhorn et al. have reported long-lasting remissions reaching up to 40% among patients with platinum-refractory disease. However, the present prospective randomized studies are heterogeneous in terms of patient characteristics and methodology, therefore superiority of HDC plus ASCR to conventional chemotherapies could not be proven. The results of the TIGER study, which is a recent prospective randomized study being conducted by the European Organisation for Research and Treatments in Cancer (EORTC) and the European Society for Blood and Marrow Transplantation (EBMT) aiming to compare HDC plus ASCR to conventional chemotherapy are eagerly expected. In this review, we will evaluate the current use of HDC plus ASCR in patients with relapsed or refractory germ cell tumors.

HLA-haploidentical transplantations for primary immunodeficiencies: a single-center experience.

SCID is characterized by profound deficiencies of T and B lymphocytes. HSCT is the only curative treatment for children with SCID. The clinical characteristics and outcome of 30 HLA-haploidentical transplantations in 18 patients (15 SCID, two Omenn syndrome, and one MHC Class II deficiency) are reported here. The age of patients at diagnosis ranged from one and half to nine months (median: four months). The median time was one month between the diagnosis and the time of the initial transplantation. Infused CD34+ stem cell dose was ranged between 7 and 94.2 × 10(6) /kg. Nine of 18 patients were found to be positive for CMV antigenemia at diagnosis; therefore, none of them received a conditioning regimen. The most common complication was graft failure (61%), so repeated transplantations (two to four) were performed in seven patients. The mean time of lymphoid engraftment was 17.5 days (median: 16, range: 11-29 days). Ten of 15 SCID (67%) patients survived with a stable complete donor chimerism. However, all three non-SCID patients died. In conclusion, in the absence of a matched family donor, HLA-haploidentical transplantation from parental donors represents a readily available treatment option especially for patients with SCID, offering a high chance of cure.

Efficacy of melatonin, mercaptoethylguanidine and 1400W in doxorubicin- and trastuzumab-induced cardiotoxicity.

Doxorubicin (DOX) and Trastuzumab (TRAST) are effective agents for the treatment of many neoplastic diseases. Cardiotoxicity is a major side effect of these drugs and limit their use. In this study, the possible protective effects of melatonin (MEL), mercaptoethylguanidine (MEG), or N-(3-(aminomethyl) benzyl) acetamidine (1400W) against the cardiotoxicity of DOX and TRAST were tested. Male Sprague-Dawley rats received an injection of DOX (20 mg/kg) alone or in combination with TRAST (10 mg/kg) to induce cardiotoxicity; daily treatments with MEL (10 mg/kg × 2), MEG (10 mg/kg × 2), or 1400W (10 mg/kg × 2) were begun 36 hr before and continued for 72 hr after DOX and TRAST administration. Oxidant/antioxidant indices of the cardiac tissue, namely, malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as serum levels of creatine phosphokinase (CK-MB) were measured. Additionally, the injury scores were evaluated histopathologically. Malondialdehyde levels were significantly higher, while SOD and GSH-Px activities were significantly reduced in rats with DOX- or DOX+TRAST-induced cardiotoxicity compared to normal values. All three treatment agents significantly reversed oxidative stress markers. Serum CK-MB levels were significantly increased after treatment with DOX and DOX+TRAST; these changes were also reversed by each of the treatments and resulted in near normal levels. Both the DOX- and DOX+TRAST-treated rats presented similar histopathologic injuries; in the animals treated with the protective agents, histologic protection of the cardiac tissue was apparent. These results suggested that MEL, MEG, as well as 1400 W are effective in preventing DOX- or DOX+TRAST-induced cardiotoxicity.

Meningeal carcinomatosis: an extremely rare involvement of urinary bladder carcinoma.

Meningeal carcinomatosis (MC) is a rare presentation of solid tumors, particularly breast cancer, lung cancer, and malignant melanoma. Recently, the incidence of MC has been reported to be increasing. It has a bad prognosis despite aggressive therapy. The usual clinical presentation is multifocal involvement of the neuraxis, with headache and radicular pain being the most common initial symptoms. The most frequent signs are motor deficits, altered mental status, and cranial nerve involvement. The treatment of MC remains controversial and no straightforward guidelines exist in the literature. MC from urinary bladder tumors is rare. In this case report, we present a 52-year-old male patient with meningeal metastasis from a primary urinary bladder carcinoma along with a review of the related literature. Free full text available at www.tumorionline.it

Oral metastasis of the mediastinal germ cell tumor (yolk sac).

A yolk sac tumor is a rare malignant tumor of germ cell origin. It most commonly arises from the testes and ovaries in young adults, but extragonadal sites of origin are reported in 10% to 15% of the cases. Yolk sac tumors are malignant, tend to recur locally, and may present with widespread metastases at the time of diagnosis. Involvement of the head and neck is uncommon. In this study, we present the case of a 23-year-old man presenting with mandibular and adjacent gingival metastasis of a mediasatinal yolk sac tumor. Thus, the patient has already undergone chemotherapy; no additional treatment was provided. In this case report, clinical and histopathologic features of the oral metastases of a yolk sac tumor were briefly discussed.

Modified outpatient dexamethazone, cytarabine and cisplatin regimen may lead to high response rates and low toxicity in lymphoma.

OBJECTIVE: Our purpose was to investigate the efficacy of and establish a toxicity profile for a modified regimen of dexamethasone, cytarabine and cisplatin (DHAP) for lymphoma outpatients. SUBJECTS AND METHODS: Fifty-one lymphoma patients, 26 with Hodgkin's disease and 25 with non-Hodgkin's lymphoma, were included. The patients' median age was 32 years (range: 17-61). Twenty had progressive/refractory disease and 31 relapsed disease. Twenty-five were in clinical stage I/II and 26 in clinical stage III/IV before the initiation of salvage chemotherapy. DHAP consisted of dexamethasone (40 mg i.v. on days 1-4), cytarabine (2 g/m(2) i.v. as 3-hour infusion on days 2 in the evening and 3 in the morning) and cisplatin (35 mg/m(2) as 2-hour infusion on days 1-3) were administered every 21 days. A total of 154 cycles of modified DHAP were administered, with a median of 3 cycles per patient (range: 2-4). RESULTS: The main toxicity was myelosuppression. WHO grade III-IV neutropenia and grade III-IV thrombocytopenia were observed in 27 (52.9%) and 21 (41%) patients, respectively. The overall response rate (85% for Hodgkin's disease and 95% for non-Hodgkin's lymphoma) was 88.3% (39.2% complete response and 49.1% partial response). CONCLUSION: The results showed that this outpatient schedule of DHAP was well tolerated and an effective salvage regimen.

Outcomes of bladder preservation therapy on survival in patients with muscle-invasive bladder cancer. / Resultados de preservación vesical en pacientes con tumor vesical musculoinfiltrante.

INTRODUCTION: The standard of care in muscle invasive bladder cancer is radical cystectomy; however; transurethral resection (TUR) followed by external radiotherapy and systemic chemotherapy demonstrates comparable results with radical cystectomy in terms of local control and survival rates. OBJECTIVES: To evaluate our results of multimodality bladder preservation therapy (BPT) in patients who had muscle-invasive bladder cancer and were reluctant to radical cystectomy. METHODS: The retrospective analysis of twenty-three patients with stage T2 transitional cell bladder cancer that were consecutively treated with BPT was performed. Treatment strategy included radical TUR followed by 3 cycles of cisplatin, gemcitabine combination, and radiotherapy of 64 Gy as adjuvant treatment. The Kaplan-Meier survival estimates and log rank were calculated. RESULTS: Median follow-up time was 58 (15-158) months. Disease-free survival (DFS) and five year overall survival (OS) rates for 23 patients were 55.9% and 63.9%, respectively. Cancer-specific OS was 67%. There were no grade 3 or higher complications. CONCLUSIONS: Our small patient group suggests that BPT can be safely applied in selected cases with bladder cancer or in patients that refused radical cystectomy.

INTRODUCCIÓN: El estándar de tratamiento en el CVMI es la cistectomía radical, aunque la RTUv + RTP+ quimioterapia sistémica demuestra resultados comparables a la cistectomía radical en términos de control local y supervivencia global. OBJETIVOS: Evaluar nuestros resultados en terapia trimodal en cáncer de vejiga músculo-invasivo que rechazan la cistectomía radical. MÉTODOS: Análisis retrospectivo de 23 pacientes con estadio T3 TVMI tratados con preservación vesical (RTUv +3 ciclos de gemcitabina, cisplatino+ 64Gy RTP adyuvante). KM estimados y log Rank fueron calculados. RESULTADOS: La mediana de seguimiento fue de 58 meses (15-158). El intervalo libre de enfermedad y la supervivencia global a los 5 anos fue de 56% y 64%, respectivamente. La Supervivencia cáncer especifica fue de 67%. No se objetivaron complicaciones grado 3 o más. CONCLUSIONES: Nuestra serie de tratamiento preservación vesical demuestra que el uso de este tratamiento en pacientes debidamente seleccionados que no quieren cistectomía radical es apropiado.

Self-reported experience of mucositis in cancer patients who underwent conditioning regimen and stem cell transplantation.

PURPOSE: This study was done to evaluate the frequency and severity of mucositis in the early period of stem cell transplantation (SCT) and the relation of conditioning regimens with mucositis. PATIENTS AND METHODS: Patients with hematologic or solid tumors who underwent conditioning regimen were asked to score mucositis severity daily from the first day to the tenth day of reinfusion. Patient-reported scoring was performed according to a five-grade scale (0: no symptom; 1: mild; 2: moderate; 3: severe; 4: very severe). Total mucositis score (TMS) was defined as the addition of daily mucositis scores for 10 days. A total of 68 SCT (58 autologous and 10 allogeneic) patients, 48 men (71%) and 20 women (29%) were included to the study. Median age of patients was 32.5 (range 15-78) years. The most frequent three diagnosis were non-Hodgkin's lymphoma (37%, n = 25), Hodgkin's lymphoma (12%, n = 8), and multiple myeloma (12%, n = 8). BEAM (n = 27), ICE (n = 17), melphelan 200 mg/m(2) (M200)(n = 8), and TBI+C (total body irradiation + cyclophosphamide) (n = 16) were used as conditioning regimens. RESULTS: All of the patients experienced mucositis at any grade. TMS in the sixth day was higher than TMS in the first day (p < 0.05). TMS was not related to the diagnosis or gender (p > 0.05). TMS at ICE regimen in the first 5 days after transplantation was more severe than BEAM regimen. TMS at TBI+C regimen was higher than TMS at BEAM regimen from day 4 to day 10 (p < 0.05). The mean percentages of patients who scored severe or very severe mucositis in 10 days was 7.4% in BEAM, 8.9% in ICE, 12.5% in M200, and 31.2% in TBI+C groups. CONCLUSION: Patients experience mucositis frequently following conditioning regimen and SCT. The necessity and the timing of prophylaxis for mucositis change due to the type of conditioning regimens.

Long-lasting multiagent chemotherapy in adult high-risk Ewing's sarcoma of bone.

The outcome of Ewing's sarcoma depends on the anatomical site of the tumor. Studies conducted in high-risk patients are limited. We evaluated the outcome of high-risk Ewing's sarcoma patients that received long-term treatment protocol. Twenty-five patients (22 males, 3 females) with poor prognostic features were treated according to long-term Ewing's sarcoma protocol. Central-axis localization, inadequacy or unavailability of surgical resection, older than 15 years of age, are accepted as high-risk factors. The median age of patients was 23 years (range, 18-55). The tumor localization was pelvis (9), femur (1), tibia (1), fibula (1), maxilla (1), clavicle (1), vertebrae (5), metatarse (1), and ribs (5). Neoadjuvant chemotherapy was applied between weeks 0 and 6, local therapy on week 9, and adjuvant maintenance chemotherapy between weeks 11 and 41. All patients received neoadjuvant and adjuvant maintenance chemotherapy. Local therapy consisted of radiotherapy (32%), surgery alone (12%), or surgery and radiotherapy (56%). The median total treatment period was 10 months. The median follow-up was 25 months (range, 7-89). Three-year cumulative OS and DFS rates were 43% (95% CI, 28.5-57.85) and 40% (95% CI 23.63-52.19), respectively. The most common grade III/IV toxicities observed during the treatment protocol were neutropenia (16%) and gastrointestinal toxicities (16%). Our study indicated that long-term multiagent combination chemotherapy may result in better outcome in adult high-risk patients undergoing adequate surgical resection of the tumor and local radiotherapy. Further randomized studies are needed to assess the efficacy of this treatment protocol in patients with adequate surgical margins.

The clinical significance of tumor cells in bone marrow or apheresis product and the efficacy of CD34+ selection and high-dose chemotherapy in patients with Stage III breast cancer.

The purpose of this study is to determine the presence of disseminated tumor cells in bone marrow or apheresis product, and also to evaluate the clinical significance of contaminated products and the efficacy of CD34(+) selection and high-dose chemotherapy in patients with Stage III breast cancer. Fifty-five patients were enrolled in this prospective cohort study. Whereas CD34(+) positive selection was not carried out in the first group (unselected group, n:31), CD34(+) positive selection was performed in the second group (CD34 selected group, n:24). Tumor cells were detected with anticytokeratin monoclonal antibody in the bone marrow, apheresis product and positive fraction. Tumor cells were found in six (19.3%) patients in unselected group and four patients (16.6%) in CD34 selected group (P = 0.76). The percentages of distant metastases were found higher in unselected group (51.6% vs. 25%, P < 0.01). Although there were no differences between the two groups for disease free survival (DFS; 44% vs. 74%, P = 0.24) or overall survival (54% vs. 68%, P = 0.84), DFS was significantly lower in patients with tumor cells than in patients without tumor cells (21% vs. 62%, P = 0.02). In conclusion, the presence of tumor cells in bone marrow or apheresis product decreases DFS in patients with Stage III breast cancer who underwent high-dose chemotherapy. CD34(+) selection does not change survivals, but it may decrease the distant metastases.

Paraneoplastic motor neuron disease resembling amyotrophic lateral sclerosis in a patient with renal cell carcinoma.

OBJECTIVE: To report an unusual paraneoplastic syndrome, amyotrophic lateral sclerosis, associated with renal cell carcinoma. CASE PRESENTATION AND INTERVENTION: A 59-year-old man presented with muscle weakness and fasciculations in the upper extremities. Neurological examination showed that the fasciculations arose spontaneously in the upper limbs. Electrodiagnostic studies revealed an active neurogenic disorder. The patient was diagnosed with a motor neuron disease mimicking amyotrophic lateral sclerosis. Urine analysis revealed microscopic hematuria. Abdominal computerized tomography scans showed a 9.5 x 8 cm renal mass in the lower pole of the right kidney. Curative right radical nephrectomy was performed. Pathologic examination showed a clear cell adenocarcinoma. After nephrectomy, the muscle weakness and fasciculations disappeared spontaneously within 2 months. The patient was disease-free for 58 months after right radical nephrectomy. He complained of muscle weakness and fasciculation at the last follow-up again. Physical examination revealed fasciculation in the upper limbs. Abdominal tomography showed a 22 x 20 mm solid mass in the lower pole of the left kidney. Kidney-saving surgery was performed and the diagnosis of renal cell carcinoma was confirmed pathologically. Following surgery, fasciculations completely disappeared and muscle weakness diminished within 3 months. CONCLUSION: This case highlights motor neuron disease as a rare paraneoplastic syndrome in association with renal cell carcinoma and resolution after removal of the tumor.

Transplantation of allogeneic hematopoietic stem cells: an emerging treatment modality for solid tumors.

Allogeneic transplantation of hematopoietic cells from an HLA-compatible donor has been used to treat hematologic malignancies. Allogeneic transplantation not only replaces the marrow affected by the disease, but exerts an immune graft-versus-tumor (GVT) effect mediated by donor lymphocytes. The development of nonmyeloablative conditioning regimens before allogeneic transplantation has allowed this therapy to be used in elderly and disabled patients. An allogeneic GVT effect is observed in a proportion of patients with renal, breast, colorectal, ovarian, and pancreatic cancer treated with allogeneic transplantation. In general, the tumor response is associated with the development of acute and chronic graft-versus-host disease. Further improvements will depend on the identification of the antigen targets of GVT, and on reduction of the toxicity of the procedure. Targeted therapies may complement the immune effect of allogeneic transplantation. We present updated results from the literature and data recently placed on file at the European Bone Marrow Transplantation Solid Tumors Working Party.

Reduced dose of lenograstim is as efficacious as standard dose of filgrastim for peripheral blood stem cell mobilization and transplantation: a randomized study in patients undergoing autologous peripheral stem cell transplantation.

In vitro studies have demonstrated a 27% increased efficacy of lenograstim over filgrastim. However, equal doses of 10 microg/kg/day of filgrastim and lenograstim have been recommended for mobilization of CD34+ cells without associated chemotherapy. In this study, we investigated whether a 25% reduced dose of lenograstim at 7.5 microg/kg/day is equavalent to 10 microg/kg/day filgrastim for autologous peripheral blood stem cell (PBSC) mobilization and transplantation. A total of 40 consecutive patients were randomized to either filgrastim (n = 20) or lenograstim (n = 20). The two cohorts were similar in regard to disease, sex, body weight, body surface area, conditioning regimens, previous chemotherapy cycles and radiotherapy. Each growth factor was administered for 4 consecutive days. The first PBSC apheresis was done on the 5th day. In the posttransplant period, the same G-CSF was given at 5 microg/kg/day until leukocyte engraftment. Successful mobilization was achieved in 95% of patients. Successful mobilization with the first apheresis, was achieved in 10/20 (50%) patients in the filgrastim group versus 9/20 (46%) patients in the lenograstim group. No significant difference was seen in the median number of CD34+cells mobilized, as well as the median number of apheresis, median volume of apheresis, percentage of CD34+ cells, and CD34+ cell number. Leukocyte and platelet engraftments, the number of days requiring G-CSF and parenteral antibiotics, the number of transfusions were similar in both groups in the posttransplant period. Lenograstim 7.5 microg/kg/day is as efficious as filgrastim 10 microg/kg/day for autologous PBSC mobilization and transplantation.

Transient efficacy of double high-dose chemotherapy and autologous peripheral stem cell transplantation, immunoglobulin, thalidomide, and bortezomib in the treatment of scleromyxedema.

Scleromyxedema is a rare disorder characterized by mucin deposits in the dermis and monoclonal gammopathy. No definitive treatment of this condition has been described to date. We present the case of a 38-year-old male patient with scleromyxedema who underwent double consecutive autologous peripheral stem cell transplantations and received immunoglobulin, thalidomide, and bortezomib. This resulted in considerable clinical and pathologic amelioration of the patient's condition. However, 3 years after the second transplant, the patient relapsed and manifested the same skin lesions evident at his initial presentation.

CD-34 selected hematopoetic stem cell transplantation from HLA identical family members for fanconi anemia.

Hematopoetic stem cell transplantation, even from an HLA 6/6 identical family member is associated with an increased frequency of complication in fanconi anemia (FA). The increased susceptibility for chromosomal breaks has been suggested as a contributory factor for increased risk of toxicity, graft versus host disease (GVHD) and increased incidence of post-transplant solid tumors. Therefore, non-irradiation based preparative regimens usually containing fludarabine and T-cell depletion of HLA geno-identical bone marrow cells have increasingly been used in patients with FA. Here, we report three children with FA who underwent CD-34 selected HSCT from HLA-identical family donors with reduced intensity fludarabine-based regimen.

The management of gastric adenocarcinoma with postoperative chemoirradiation. A non-randomized comparison of oral UFT and 5-FU.

AIMS AND BACKGROUND: We assessed the therapeutic results and tolerability of postoperative chemoradiotherapy with either oral UFT or 5-fluorouracil for carcinoma of the stomach. METHODS AND STUDY DESIGN: Forty-six patients treated with chemoradiotherapy following total or subtotal gastrectomy for gastric carcinoma formed the cohort evaluated. The group included 39 males and 7 females whose ages ranged from 21 to 74 years (median, 53 years). In all patients, surgical therapy was the initial approach with a curative intent. The types of operations performed were total gastrectomy in 11 or subtotal gastrectomy in 35 patients. Radiotherapy began from 14 to 161 days after surgery (median, 55 days). Twenty patients received concomitant oral UFT (200 mg/m2), and 26 patients were given 5-fluorouracil (425 mg/m2, iv bolus) concurrently with irradiation consisting of one or two cycles, usually as a 3-day bolus at the start and last 3 days of irradiation therapy for radiosensitizing purposes. The patients were treated using either cobalt-60 or 6 MV photons, and irradiation doses delivered to the tumor bed and regional lymphatics ranged from 40 to 50 Gy (median, 46 Gy). RESULTS: Median follow-up for the entire group was 24 months (range, 2-67). The 2-year overall survival of the entire group of patients was 64%. The 2-year overall survival rates for 5-fluorouracil and oral UFT groups were 72% and 66%, respectively (P = 0.3). Treatment-related factors were reviewed to identify any impact on survival. Analyses included type of surgery and dissection, fraction size, the total dose of irradiation and the type of chemotherapy. A significant detrimental effect in survival in the patients treated with D2 dissection compared to the patients treated with D1 dissection was noted (P = 0.01). Overall grade II-III toxicity of oral UFT was significantly lower than 5-FU (4 patients vs 14 patients, P = 0.03). CONCLUSIONS: Concomitant use of oral UFT with radiation seems to be more tolerable and an equally effective regimen in the treatment of locally advanced gastric cancer compared with 5-fluorouracil. D2 dissection was found to have detrimental effects on survival in this cohort.

Acute renal toxicity of 2 conditioning regimens in patients undergoing autologous peripheral blood stem-cell transplantation. Total body irradiation-cyclophosphamide versus ifosfamide, carboplatin, etoposide.

OBJECTIVE: To compare acute renal toxicity of 2 conditioning regimens of total body irradiation/cyclophosphamide (TBI-Cy) and Ifosfamide, Carboplatin, and Etoposide (ICE). METHODS: Between August 1996 and February 2004, patients treated with autologous peripheral stem cell transplantation in the Department of Medical and Radiation Oncology, Gulhane Military Medical School, Ankara, Turkey with 2 different conditioning regimens was comparatively analyzed for acute renal toxicity in the early post-transplant period. Forty-seven patients received ICE regimen with 12 g/m2; 1.2 g/m2; and 1.2 g/m2 divided to 6 consecutive days, whereas 21 patients received 12 Gy TBI (6 fractions twice daily in 3 consecutive days) and 60 mg/m2/day cyclophosphamide for 2 days. RESULTS: Sixty-eight patients were evaluated in this study. There was no significant difference in baseline renal function between patients in the ICE and TBI-Cy groups. Eleven patients developed nephrotoxicity (23.4%) in the ICE group while one patient (4.8%) in the TBI-Cy group developed nephrotoxicity (p=0.06). Five out of 11 patients developing nephrotoxicity in ICE group required hemodialysis and subsequently 4 (8.5%) of them died. In contrast, one patient (4.8%) died due to nephrotoxicity despite hemodialysis in the TBI-Cy arm. CONCLUSION: This study reveals that the TBI-Cy conditioning regimen seems no more nephrotoxic than an ICE regimen particularly in patients who had used cisplatin prior to transplantation.

A Review of Allogeneic Hematopoietic Stem Cell Transplantation in Metastatic Breast Cancer.

Breast cancer (BC) has a high mortality rate and metastatic BC is almost incurable despite hormonal therapy and chemotherapy. The second and third lines of chemotherapies usually yield transient responses and the median survival is generally as low as 18-24 months. Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) have been extensively investigated in this setting. The presence of immune mediated anti-tumor effects referred to as graft-versus-tumor (GvT) effects after allogeneic HSCT among patients with solid tumors have been clearly defined. The advantages of allogeneic HSCT over autologous HSCT for metastatic BC are i) cancer-free graft and ii) immune-mediated GvT effects mediated by human leukocyte antigen compatible donor T-cells. In conclusion, a GvT effect does exist against metastatic BC and play a key role in tumor response. This review aims to describe the background, rationale, and clinical results of allogeneic HSCT as a potential alternative treatment in metastatic BC.