High-Dose Chemotherapy in Poor-Prognosis Adult Small Round-Cell Tumors: Clinical and Molecular Results From a Prospective Study

2002 ◽  
Vol 20 (8) ◽  
pp. 2181-2188 ◽  
Author(s):  
Alexia Bertuzzi ◽  
Luca Castagna ◽  
Andrea Nozza ◽  
Vittorio Quagliuolo ◽  
Licia Siracusano ◽  
...  

PURPOSE: The prognosis of metastatic/high-risk localized small round-cell tumors (SRCTs) treated conventionally is dismal. In this phase II study, we explored a high-dose chemotherapy (HD-CT) approach and analyzed the clinical significance of fusion transcripts detection. PATIENTS AND METHODS: From June 1997 to November 1999, 28 SRCT patients (median age, 26 years; 14 peripheral primitive neuroectodermal tumors [pPNETs], seven rhabdomyosarcomas [RMSs], and seven desmoplastic small round-cell tumors [DSRCTs]) received induction chemotherapy with ifosfamide, epirubicin, and vincristine followed by HD-CT. Local treatment (radiotherapy and/or surgery) was performed when possible. Molecular analysis was performed on peripheral-blood and leukapheresis products by reverse-transcriptase polymerase chain reaction. RESULTS: Overall response (OR) was 65% (18 of 28), with 40% complete response and 25% partial response. According to histology, the OR rate was 86% in pPNET and 43% in both RMS DSRCT. With a median follow-up of 35 months, median overall survival was 16 months and median progression-free survival (PFS) was 10 months. PFS was statistically better in pPNET than other histologic types (P = .0045). No correlation was found between the fusion transcript and clinical outcome during follow-up. Furthermore, transcript detection in leukapheretic products was not of prognostic significance. CONCLUSION: Intensive HD-CT seems to enhance the response rate and survival when compared with conventional treatment in poor-prognosis pPNET. The poor results of this treatment in RMS and DSRCT do not support the inclusion of such an approach in these patient subsets. No definitive conclusions can currently be drawn concerning the clinical implications of the detection of fusion transcripts during treatment or follow-up.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5086-5086
Author(s):  
Joanna Yeung ◽  
Sara Samiee ◽  
Qi Long Yi ◽  
Dominic Pantalony ◽  
Hong Chang

Abstract CD56 is a neural adhesion molecule and expressed in 70–80% cases of multiple myeloma (MM). Lack of CD56 expression has shown to be a poor prognosis in MM patients treated with conventional chemotherapy, but its prognostic relevance in MM treated with high dose chemotherapy and autologous stem cell transplant (ASCT) is not known. CD56 expression was evaluated by immunohistochemistry on bone marrow paraffin embed specimens from 107 MM cases undergoing Melphalan-based high dose therapy and ASCT. The 66 men and 41 women had a median age of 54 years. 53 patients had an IgG paraprotein, 30 IgA, 4 IgD, 15 light chain disease and 5 were nonsecretory. The median post-transplant follow-up was 20 months. Of 107 MM patients, 76 (71%) were CD56 positive and 31 negative. 27 died during the follow-up period including 7(23%) in CD56 negative and 20 (26%) in CD56 positive group; 50 were in relapse including 11 (35%) in CD56-negative, and 39 (51%) in CD56 positive group. The median overall survival for the CD56 positive patients was 48.1 months and for the CD56 negative patients, 44.8 months (p=0.67). The median progression free survival of the CD56 positive patients was 25.8 months and for the CD56 negative patients, 33.1 months (p=0.28). CD56 negative myeloma was associated with bone lesions (69% for CD56 positive vs 90% for CD56 negative group, p=0.032). However, CD56 was not associated with other biological factors including age, sex, hemoglobin, calcium, albumin, c-reactive protein, beta-2 microglobulin, immunoglobulin isotype, stage of the disease or bone marrow plasmacytosis. Furthermore, there was no correlation between CD56 expression and genetic aberrations including deletions of 13q14, 17p13.1 (p53), translocations t(11;14) or t(4;14) as evaluated by fluorescence in situ hybridization (FISH). In contrast to reports of CD56 in myeloma treated with conventional chemotherapy, we found CD56 negativity does not confer a poor prognosis in our patients, suggesting Melphalan-based high-dose chemotherapy and ASCT may overcome the adverse influence of CD56 negative myeloma.


1999 ◽  
Vol 17 (1) ◽  
pp. 82-82 ◽  
Author(s):  
Russell L. Basser ◽  
L. Bik To ◽  
John P. Collins ◽  
C. Glenn Begley ◽  
Dorothy Keefe ◽  
...  

PURPOSE: To determine the safety and efficacy of multiple cycles of dose-intensive, nonablative chemotherapy in women with poor-prognosis breast cancer. PATIENTS AND METHODS: Women with stage II breast cancer and 10 or more involved nodes or four or more involved nodes and estrogen receptor–negative tumors and women with stage III disease received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2, with progenitor cell and filgrastim support every 28 days (n = 79) or 21 days (n = 20). Patients were reviewed at least twice yearly thereafter. Twenty-six patients had bone marrow and apheresis collections assessed for the presence of micrometastatic tumor cells. RESULTS: Ninety-nine women (median age, 43 years; range, 24 to 60 years) were treated. Ninety-two completed all three cycles of chemotherapy. The major toxicity was severe, reversible myelosuppression that was more prolonged with successive cycles, and this did not differ between patients given treatment every 28 days and those treated every 21 days. Febrile neutropenia occurred in 176 (61%) of 287 cycles. Severe mucositis (grade 3 or 4) occurred in 23% of cycles but tended to be short-lived and was reversible. The cardiac ejection fraction fell by a median of 4% during treatment, and three patients developed evidence of cardiac failure after chemotherapy. Two patients (2%) died of acute toxicity. Three of 26 patients had evidence of circulating micrometastatic tumor cells. The actuarial distant disease-free and overall survival rates at 60-month follow-up were 64% (95% confidence interval [CI], 53% to 75%) and 67% (95% CI, 56% to 78%), respectively. CONCLUSION: Multiple cycles of dose-intensive, nonablative chemotherapy is a feasible and safe approach. Disease control and survival are similar to those in other studies of myeloablative chemotherapy in poor-prognosis breast cancer. The regimen is being evaluated in a randomized trial of the International Breast Cancer Study Group.


Author(s):  
R. Luque ◽  
M. Benavides ◽  
S. del Barco ◽  
L. Egaña ◽  
J. García-Gómez ◽  
...  

AbstractRecent advances in molecular profiling, have reclassified medulloblastoma, an undifferentiated tumor of the posterior fossa, in at least four diseases, each one with differences in prognosis, epidemiology and sensibility to different treatments. The recommended management of a lesion with radiological characteristics suggestive of MB includes maximum safe resection followed by a post-surgical MR < 48 h, LCR cytology and MR of the neuroaxis. Prognostic factors, such as presence of a residual tumor volume > 1.5 cm2, presence of micro- or macroscopic dissemination, and age > 3 years as well as pathological (presence of anaplastic or large cell features) and molecular findings (group, 4, 3 or p53 SHH mutated subgroup) determine the risk of relapse and should guide adjuvant management. Although there is evidence that both high-risk patients and to a lesser degree, standard-risk patients benefit from adjuvant craneoespinal radiation followed by consolidation chemotherapy, tolerability is a concern in adult patients, leading invariably to dose reductions. Treatment after relapse is to be considered palliative and inclusion on clinical trials, focusing on the molecular alterations that define each subgroup, should be encouraged. Selected patients can benefit from surgical rescue or targeted radiation or high-dose chemotherapy followed by autologous self-transplant. Even in patients that are cured by chemorradiation presence of significant sequelae is common and patients must undergo lifelong follow-up.


2015 ◽  
Vol 45 (9) ◽  
pp. 1308-1315 ◽  
Author(s):  
Austin Ostermeier ◽  
M. Beth McCarville ◽  
Fariba Navid ◽  
Scott E. Snyder ◽  
Barry L. Shulkin

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