Efficacy of high-dose therapy and autologous hematopoietic stem cell transplantation for non-Hodgkin's lymphoma in adults 60 years of age and older

To evaluate autologous stem cell transplant (ASCT) in older patients with intermediate grade non-Hodgkin's lymphoma (NHL), the Mayo Clinic Rochester BMT database was reviewed for all patients 60 years of age and older who received ASCT for NHL between September 1995 and February 2003. Factors evaluated included treatment-related mortality (TRM), event-free survival (EFS) and overall survival (OS). Ninety-three patients were identified, including twenty-four (26%) over the age of 70 years. Treatment-related mortality (5.4%) was not significantly different when compared to a younger cohort (2.2%). At a median follow-up of 14 months (0.6-87.6 months), the estimated median survival is 25 months (95% confidence interval (CI) 12-38) in the older group compared to 56 months (95% CI 37-75) (P ¼ 0.037) in the younger group. The estimated 4-year EFS was 38% for the older group compared to 42% in the younger cohort (P ¼ 0.1). By multivariate analysis, the only factor found to influence survival in the older group was ageadjusted International Prognostic Index at relapse, 0-1 better than 2-3 (P ¼ 0.03). Autologous stem-cell transplant can be safely performed in patients 60 years or older with chemotherapy sensitive relapsed or first partial remission NHL. The outcome may not be different from that of younger patients in terms of TRM and EFS.

Section: Discussionmentioning

confidence: 99%

“…11,12 Similarly, a number of recent studies have demonstrated that ASCT can be safely carried out in older patients with NHL, with reasonable response rates, acceptable toxicity and minimal transplant-related mortality. [13][14][15][16][17] These studies, while informative, were limited by their small size.…”

Section: Introductionmentioning

confidence: 99%

Autologous hematopoietic stem cell transplantation for older patients with relapsed non-Hodgkin's lymphoma

Buadi

Micallef

Ansell

et al. 2006

“…There are no conclusive data to recommend one conditioning regimen over another in this population. [7][8][9]26 We have demonstrated that a modified BU and CY regimen in selected patients X60 years of age is well tolerated. The dose of BU has been reduced to 14 doses of 0.8 mg/kg i.v.…”

Section: Discussionmentioning

confidence: 99%

Autologous SCT with a dose-reduced BU and CY regimen in older patients with non-Hodgkin's lymphoma

Yusuf

Dey

Yeap

et al. 2008

Autologous SCT is a potentially curative procedure for patients with relapsed lymphoma (NHL). We analyzed the outcomes of 34 patients X60 years old, including eight patients X70 years old, who received BU and CY and SCT for NHL. Patients received BU 0.8 mg/kg i.v. (n ¼ 25) or 1 mg/kg p.o. (n ¼ 9) q 6 h Â 14 doses and CY 60 mg/kg i.v. q day Â 2 days. The median age was 66 (range, 60-78) years. Twenty-two patients had large cell, 10 follicular and two-mantle cell lymphoma. Fifteen patients were in a second or greater CR and 19 patients were in a PR. The median days to ANC 4500/ll and platelet count 450 000/ll were 10 and 13 days respectively. The 100-day transplant-related mortality was 0%. Toxicities included interstitial lung disease (n ¼ 2), seizures in a patient with CNS lymphoma (n ¼ 1), mild veno-occlusive disease (n ¼ 2), and transient atrial fibrillation (n ¼ 4). With a median follow-up of 40 months, the 2-year overall survival and PFS were 67 and 54% respectively. BU/CY is a well-tolerated conditioning regimen for older patients with NHL. Age alone should not be used as an exclusion criterion for autologous SCT.

“…15,16 This regimen was also employed by Soussain's group in treating relapsed PCNSL. 13,14 Busulfan achieves therapeutic levels in CSF and in brain parenchyma in animal models.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, this combination of agents has been well studied in high dosage. [13][14][15][16] Patients and methods…”

mentioning

confidence: 99%

High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma

Cheng

Forsyth

Chaudhry

et al. 2003

124

Summary:Treatment of primary central nervous system lymphoma (PCNSL) with combined high-dose methotrexate (HD-MTX)-based chemotherapy and whole-brain radiotherapy (WBRT) is associated with severe neurotoxicity, but high relapse rates are associated with the use of either modality alone. In an attempt to improve upon these dismal results, we treated seven PCNSL patients with HD-MTX-based induction therapy followed by thiotepa, busulfan, cyclophosphamide (TBC), and autologous stem cell transplant (ASCT), without WBRT. Six of these patients had at least one of the following poor prognostic features: Karnofsky performance status (KPS) p50%, age 460 years, or relapsed disease. All but one patient tolerated the treatment well and experienced improvements in neurological function and overall performance status posttransplant. No treatment-induced neurotoxicity (dementia, ataxia, and incontinence) was observed although the follow-up is short. One early treatment-related death occurred in a patient with multiple comorbid medical conditions. The other six patients achieved a complete response (CR) after TBC and ASCT. Five patients are currently alive and relapse-free at 5, 8, 24, 36, and 42 months from diagnosis. One additional patient relapsed and died 33 months after diagnosis. Two of the seven patients received TBC/ASCT as the only treatment after disease progression following their initial chemotherapy and both remain relapse-free at the time of this report, 22 and 31 months post-TBC/ASCT. In conclusion, prolonged CR can be attained after chemotherapy-only treatment of poor prognosis PCNSL. Furthermore, this small series suggests that high-dose chemotherapy for PCNSL should include drugs that penetrate the CNS such as busulfan and thiotepa rather than standard lymphoma regimens such as BEAM.