Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results

Abstract

In 2008, we reported favorable 5-year outcomes of nonmyeloablative allogeneic stem cell transplantation after fludarabine, cyclophosphamide, rituximab (FCR) conditioning for relapsed and chemosensitive follicular lymphoma. However, innovative strategies were still needed to treat patients with chemorefractory disease. We therefore subsequently performed a trial in which 90 Y-ibritumomab tiuxetan (0.4 mCi/kg) was added to the fludarabine, cyclophosphamide conditioning regimen ( 90 YFC). Here, we report updated results of the FCR trial and outcomes after 90 YFC. For the FCR group (N ‫؍‬ 47), since the last update, one patient developed recurrent disease. With a median follow-up of 107 months (range, 72-142 months), the 11-year overall survival and progression-free survival rates were 78%, and 72%, respectively. For the 90 YFC group (N ‫؍‬ 26), more patients had chemorefractory disease than did those in the FCR group (38% and 0%, P < .001). With a median follow-up of 33 months (range,17-94 months), the 3-year progression-free survival rates for patients with chemorefractory and chemosensitive disease were 80% and 87%, respectively (P ‫؍‬ .7). The low frequency of relapse observed after a long follow-up interval of 9 years in the FCR group suggests that these patients are cured of their disease. The addition of 90 Y to the conditioning regimen appears to be effective in patients with chemorefractory disease. This trial was registered at www.clinicaltrials.gov as NCT00048737.

Fludarabine and treosulfan compared with other reduced-intensity conditioning regimens for allogeneic stem cell transplantation in patients with lymphoid malignancies

“…23,24 NRM is lower after RIC, in the range of 20-35%, which is still higher than NRM after RIC in AML/myelodysplastic syndromes. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] This is possibly related to patients with lymphoma been older and more heavily treated at the time of SCT including a high incidence of prior autologous SCT. In the current study NRM was relatively low after FT and FB2, both 24%, similar to RIC regimens, whereas it was 54% after FM which is more similar to MAC regimens.…”

“…Indolent lymphoma is usually associated with better outcome due to more effective graft-versus lymphoma effect and a lesser need for intensive chemotherapy to control disease until it becomes effective. 15 Patients with diffuse large B-cell lymphoma, who relapse after autologous SCT have a very poor prognosis with standard chemotherapy. Responses are not common, short and 1-year survival is 11%.…”

“…Survival rates in the range of 20-52% have been reported in other, smaller studies depending on patient characteristics at SCT. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Chemo-refractory disease is the most important predicting factor for survival across all studies. However, a small subset of patients with refractory lymphoma can achieve long-term survival with allogeneic SCT with both MAC and RIC.…”

“…Reduced intensity (RIC) and nonmyeloablative (NMA) conditioning regimens have allowed marked reduction in NRM and extension of the indications and patient groups able to tolerate treatment. [11][12][13][14][15][16][17] More than two thirds of patients with lymphoid malignancies are currently offered these regimens. 18 Although patients with myeloid malignancies are often selected for RIC based on age, comorbidities and disease status, 19 patients with lymphoid malignancies are often selected for RIC based on the disease type alone.…”

Allogeneic hematopoietic cell transplantation as curative therapy for non-transformed follicular lymphomas

“…The results of several, but not all clinical trials show low NRM and high OS, and event-free survival (EFS) rates after RIC as compared with MAC in FL. [24][25][26][27][28][29][30][31] The present retrospective study enrolled a large cohort of intensively pretreated patients who received HCT for nontransformed histological grades 1-3A FL. The aim of the study was to identify prognostic factors for transplantation outcome, that is, to define subgroups of FL patients who will or will not benefit from transplantation.…”