Cancer Research Highlights: High-Dose Chemo Plus Autologous Stem Cell Transplantation Boosts Event-Free Survival in Some Patients with Aggressive NHL

2004 ◽  
Author(s):  
Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 940-940 ◽  
Author(s):  
Chang-Ki Min ◽  
Hwak Kim ◽  
Kihyun Kim ◽  
Jae-Yong Kwak ◽  
Seung Tae Lee ◽  
...  

Abstract Background: Autologous stem-cell transplantation (ASCT) after high-dose chemotherapy is regarded as the standard therapeutic approach for multiple myeloma (MM) even if virtually all patients ultimately relapse following this procedure. Recently, tandem ASCT significantly improved overall survival (OS) and event-free survival (EFS) compared with single ASCT. Another strategy is to use reduced-intensity allogeneic stem cell transplantation (RISCT) earlier in the course of disease in chemosensitive patients. In the current study, we retrospectively analyzed the outcomes after a planned tandem ASCT or RISCT in the patients who previously underwent ASCT. Patients and methods: One-hundred twenty-six patients who received a high dose (140 to 200 mg/m2) of melphalan as the conditioning regimen of the first ASCT were analyzed. Ninety-six patients (median age, 50.5 years) received a second ASCT, whereas 30 patients (median age, 46.5 years) underwent a RISCT (related in 28 patients and unrelated in 2 patients). The median interval between the first and second transplant was 131 days in tandem ASCT group and 157.5 days in RISCT group. The conditioning regimen for the tandem ASCT and RISCT consisted of high-dose melphalan ± total body irradiation (TBI) and fludarabine + melphalan or TBI, respectively. The two groups were evenly matched with regard to other disease characteristics. Results: After a median follow-up of 664 days (range, 143–2904) from the first ASCT, the median event-free survival (EFS) and overall survival (OS) in all 126 patients were 878 days and 1838 days, respectively. The median EFS in the second ASCT vs. RISCT group were 844 days (95% CI, 714–973) and 1342 days (95% CI, 813–1870), respectively (P=0.262). The median OS in the tandem ASCT vs. RISCT group were 2160 days (95% CI, 1847–2832) and 1575 days (95% CI, 1202–1947), respectively (P=0.132). Disease-related mortality was not significantly different between the second ASCT vs. RISCT groups (73.3% vs. 60.0%, P=0.325) as well as treatment-related mortality between the 2 groups (26.7% vs. 40%, P=0.358). On multivariate analysis, an achieving a good response (≥ VGPR) after the induction treatment predicted a better EFS compared to a poor response (≤ PR) (RR; 0.245, P=0.01). A good response after first ASCT or the second transplant was associated with a better EFS by univariate analysis but not by multivariate analysis (RR; 0.927, P=0.830 or RR; 0.772, P=0.453, respectively). Conclusion: In this retrospective analysis, ASCT followed by RISCT was not superior to the tandem ASCT, either EFS or OS. Disease-related deaths were not different between the 2 groups. Patients whose disease is sensitive to induction chemotherapy and who obtain a good response after the induction treatment benefited the most from this tandem transplant therapy.


Cancer ◽  
2007 ◽  
Vol 109 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Steéphane Vignot ◽  
Nicolas Mounier ◽  
Jeérôme Larghero ◽  
Pauline Brice ◽  
Laurent Quero ◽  
...  

2005 ◽  
Vol 23 (16) ◽  
pp. 3793-3801 ◽  
Author(s):  
Gustaaf W. van Imhoff ◽  
Bronno van der Holt ◽  
Marius A. MacKenzie ◽  
Mars B. van′t Veer ◽  
Pierre W. Wijermans ◽  
...  

Purpose Timing, appropriate amount, and composition of treatment before high-dose therapy and autologous stem-cell transplantation (ASCT) in patients with poor-risk, aggressive non-Hodgkin's lymphoma (NHL) are still unknown. We conducted two consecutive multicenter phase II trials with up-front, high-dose, sequential chemotherapy and ASCT in poor-risk, aggressive NHL. Both trials had identical inclusion criteria and only differed in amount and duration of induction treatment before ASCT. Patients and Methods Between 1994 and 2001, 147 newly diagnosed, poor-risk, aggressive NHL patients, age ≤ 65 years with stage III to IV and lactate dehydrogenase (LDH) more than 1.5× upper limit of normal (ULN), entered the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) -27 and HOVON-40 trials. Treatment in HOVON-27 consisted of two up-front, high-dose induction courses followed by carmustine, etoposide, cytarabine, and melphalan plus ASCT in responding patients. In HOVON-40, the same treatment was preceded by three intensified courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Results Patient characteristics in both trials were comparable: 80% had diffuse large B-cell lymphoma, 77% had stage IV disease, and median LDH levels were 3.1× ULN. Complete remission (CR) in both trials was 45% to 51%. Before ASCT, CR was 14% in HOVON-27 versus 28% in HOVON-40 (P = .03). Treatment failure was similar (27%). Four-year survival estimates in HOVON-27 compared with HOVON-40 were overall survival, 21% v 50% (P = .007); event-free survival, 15% v 49% (P = .0001); and disease-free survival, 34% v 74% (P = .008). This different outcome favoring HOVON-40 remained highly significant when correcting for competing risk factors in multivariate analysis. Conclusion In patients with poor-risk, aggressive NHL, addition of intensified CHOP before up-front, high-dose, sequential therapy and ASCT significantly improved the duration of response and survival.


Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1260-1265 ◽  
Author(s):  
A Kessinger ◽  
JO Armitage ◽  
DM Smith ◽  
JD Landmark ◽  
PJ Bierman ◽  
...  

Abstract Forty patients with refractory Hodgkin's disease (24 patients) or non- Hodgkin's lymphoma (16 patients) who were considered for high-dose therapy but not for autologous bone marrow transplantation (ABMT) due to BM metastases, previous pelvic irradiation, a history of marrow involvement by tumor or hypocellular marrow in conventional harvest sites received high-dose therapy and autologous peripheral blood (PB) hematopoietic stem cell transplantation. Disappearance of circulating neutrophils and development of RBC and platelet transfusion-dependence was followed, in the evaluable patients, by reappearance of 0.5 x 10(9)/L circulating granulocytes and sufficient platelets to obviate the need for platelet transfusions at a median of 25 days after transplantation. Twenty-three patients experienced a clinical complete remission (CR). The projected 2-year event-free survival was 24% for all 40 patients and 49% for the non-Hodgkin's lymphoma patients. The projected 18-month event-free survival for the Hodgkin's disease patients was 15%. PB stem cell transplantation provided an opportunity to administer high-dose salvage therapy to patients with refractory lymphoma who otherwise were not candidates for such therapy. For some of those patients, the high-dose therapy produced prolonged survival, free of tumor progression.


2008 ◽  
Vol 26 (2) ◽  
pp. 218-224 ◽  
Author(s):  
Charalampia Kyriakou ◽  
Carmen Canals ◽  
Anthony Goldstone ◽  
Dolores Caballero ◽  
Bernd Metzner ◽  
...  

PurposePatients with angioimmunoblastic T-cell lymphoma (AITL) have poor prognoses with current conventional chemotherapy. The aim of this study was to evaluate the effect of high-dose therapy (HDT) followed by autologous stem-cell transplantation (ASCT) on patients with AITL.Patients and MethodsWe report a retrospective, multicenter study of 146 patients with AITL who received ASCT. The source of the stem cells was peripheral blood in 143 patients. The conditioning regimen varied, and 74% of the patients received carmustine and 1,3-bis(2-chloroethyl)-1-nitrosourea; etoposide; ara-C; and melphalan chemotherapy.ResultsAfter a median follow-up of 31 months (range, 3 to 174 months), 95 patients (65%) remained alive, and 51 patients (35%) died. Forty-two patients died as a result of disease progression, and nine died as a result of regimen-related toxicity. The cumulative incidence of nonrelapse mortality was 5% and 7% at 12 and 24 months, respectively. The actuarial overall survival (OS) was 67% at 24 months and 59% at 48 months. The cumulative incidence of relapse was estimated at 40% and 51% at 24 and 48 months, respectively. Disease status at transplantation was the major factor that impacted outcome. Patients who received a transplant during first complete remission (CR) had significantly superior progression-free survival and OS. The estimated PFS rates for patients who received their transplants in CR were 70% and 56% at 24 and 48 months, respectively; 42% and 30% for patients with chemotherapy-sensitive disease at those time points, respectively; and 23% at both time points for patients with chemotherapy-refractory disease.ConclusionThis study shows that HDT and ASCT offers the possibility of long-term disease-free survival to patients with AITL. Early transplantation is necessary to achieve optimal results.


Blood ◽  
1991 ◽  
Vol 77 (11) ◽  
pp. 2322-2325 ◽  
Author(s):  
A Kessinger ◽  
PJ Bierman ◽  
JM Vose ◽  
JO Armitage

Abstract Between February 1986 and March 1990, 56 patients with relapsed Hodgkin's disease treated with high-dose cyclophosphamide, carmustine, and etoposide (CBV) received an autologous peripheral stem cell transplantation (PSCT) rather than an autologous bone marrow transplantation (ABMT) because each patient had a marrow abnormality, either hypocellularity or tumor involvement. At least 6.5 x 10(8) [corrected] mononuclear cells/kg patient weight were collected from the peripheral blood of each patient, cyropreserved, and returned intravenously following CBV administration. Three patients had an early death 2, 22, and 25 days after PSCT. The actuarial event-free survival for these 56 patients at 3 years was 37% and was at least as good as that reported for relapsed Hodgkin's disease patients treated with CBV and ABMT. The 30 patients who had no marrow metastases at the time of PSC harvesting had an actuarial event-free survival of 47%, while those 26 patients with marrow metastases had a significantly different actuarial event-free survival of 27% (P = .02). CBV and PSCT for patients with relapsed Hodgkin's diseases who have marrow hypocellularity in traditional harvest sites or histopathologic evidence of BM metastases can result in long-term event-free survival.


1994 ◽  
Vol 12 (9) ◽  
pp. 1890-1901 ◽  
Author(s):  
D R Adkins ◽  
D Salzman ◽  
D Boldt ◽  
J Kuhn ◽  
R Irvin ◽  
...  

PURPOSE We investigated the feasibility of escalating doses of dacarbazine (DTIC) in combination with high-dose cyclophosphamide, carmustine, and etoposide (CBV) given with autologous stem-cell transplantation in 33 patients with relapsed or refractory lymphoma or multiple myeloma. PATIENTS AND METHODS Eligible patients were treated in this phase I study with cyclophosphamide (7.2 g/m2), carmustine (BCNU) (600 mg/m2), etoposide (2.4 g/m2), and escalating doses of DTIC (3,000 to 6,591 mg/m2) administered either as a 2- (in 23 patients) or a 6- (in 10 patients) hour infusion to determine the maximum-tolerated dose (MTD) of DTIC and the toxicity profile of this combination. RESULTS The MTD of DTIC infused over 2 hours and given with the CBV regimen was 3,900 mg/m2, with the dose-limiting toxicity being hypotension. Seven patients experienced transient acute hypocalcemia in association with the DTIC infusion. Prolonging the DTIC infusion to 6 hours or administration of supplemental calcium did not allow further dose escalation of DTIC to occur. Other non-hematologic toxicities observed with this regimen have been reported with CBV alone. Of 25 patients assessable for tumor response at first evaluation posttransplant, 13 (52%) were in complete remission (CR), four (16%) were in partial remission (PR), five (20%) had stable disease (SD), and three (12%) had progressive disease (PROG). Of 31 patients assessable for relapse-free survival, 22 are alive with 13 in CR, one in PR, two with SD, and six with PROG at a median follow-up duration of 313 days (range, 35 to 749+). Treatment-related mortality occurred in six patients (18%). CONCLUSION The feasibility of combining DTIC in high doses with the CBV regimen has been demonstrated. Dose-limiting hypotension is transient and reversible when DTIC is administered at 3,900 mg/m2 with CBV. Future trials to evaluate the effect of the addition of DTIC to the CBV regimen on response rate and relapse-free survival are encouraged.


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