High-dose therapy with autologous haematopoietic support in patients with transformed follicular lymphoma: A study of 27 patients from a single centre

Foran, James M.; Apostolidis, John; Papamichael, D.; Norton, A. J.; Matthews, Janet; Amess, J. A. L.; Lister, T. A.; Rohatiner, A. Z. S.

doi:10.1023/a:1008349427337

Cited by 77 publications

(45 citation statements)

References 23 publications

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“…17,18 Several later studies with limited numbers of patients have not shown a difference in outcomes, potentially secondary to inadequate power. 11,12,16,19,20 Only one study of 50 patients with transformed disease demonstrated no difference in outcomes indirectly, comparing the patients to historical controls with de novo follicular or de novo large cell lymphoma. 21 In our cohort of 49 patients, among whom 22 had transformed disease, histologic transformation was not a statistically significant predictor of OS or EFS by multivariable analysis.…”

Section: Discussionmentioning

confidence: 99%

Long-term event-free survivors after high-dose therapy and autologous stem-cell transplantation for low-grade follicular lymphoma

Andreadis

Schuster

Chong

et al. 2005

Bone Marrow Transplant

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Summary:Although follicular lymphoma (FL) is generally responsive to conventional-dose chemotherapy, improved survival in patients with this disease has been difficult to demonstrate. High-dose chemo/radiotherapy followed by autologous stem-cell transplantation (ASCT) can improve response rates, although its effects on survival remain controversial. Between 1990 and 2003, we transplanted 49 patients with low-grade FL at our institution. Twenty-two patients (45%) had undergone histologic transformation at the time of ASCT. In all, 44 patients (90%) had relapsed disease and five patients (10%) were resistant to chemotherapy at the time of transplantation. After ASCT, 30 patients (61%) were in complete remission (CR). The median overall survival (OS) has not been reached, while the median event-free survival (EFS) is 2.4 years. At a median follow-up of 5.5 years (longest 12.4 years), a plateau has been reached with 56% of patients remaining alive, and 35% event-free. ASCT was well tolerated except for two (4%) treatment-related deaths. In multivariable analysis, CR after ASCT and age less than 60 years are the best predictors of EFS and OS. ASCT is thus a safe therapeutic approach in FL, resulting in long-term EFS and OS for some patients, even with transformed disease. Bone Marrow Transplantation (2005) 36, 955-961.

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Section: Discussionmentioning

confidence: 99%

Long-term event-free survivors after high-dose therapy and autologous stem-cell transplantation for low-grade follicular lymphoma

Andreadis

Schuster

Chong

et al. 2005

Bone Marrow Transplant

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“…There have been several studies investigating intensive chemotherapy regimens with autologous stem cell support in an effort to improve response and survival [36][37][38][39][40][41][42][43][44] (Table 4). In 1989, Schouten et al 38 reported 10 patients who had undergone autologous transplantation for HT at the University of Nebraska.…”

Section: Autologous Transplantationmentioning

confidence: 99%

“…In addition to TRM, outcomes from autologous transplantation are adversely affected by a 2-15% incidence of second malignancies, predominantly MDS and AML. 9,[38][39][40][41] Though the small absolute numbers precluded analysis, several investigators proposed the cause to be the cumulative risk of alkylating agents and TBI. With the 3 cases of MDS in Berglund's series occurring at 4, 5, and 7 years post-transplant, the concern for increasing incidence of MDS/AML with longer follow-up time arises.…”

Section: Autologous Transplantationmentioning

confidence: 99%

Transformed lymphoma: an Achilles' heel of non-Hodgkin's lymphoma

Lerner

Burns

2003

Bone Marrow Transplant

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“…[4][5][6][7][8] This event typically carries a poor prognosis, 2,7 although durable remissions have been observed in a subset of individuals following high-dose therapy. 9,10 Transformation provides an important model for the study of oncogenesis and a number of recurring secondary events are recognised that may be of mechanistic significance. These include acquisition of recurrent chromosomal aberrations including loss of 17p and gains at 12q, [11][12][13][14] inactivation of CDKN2A and CDKN2B, 15 dysregulation of c-MYC 16,17 and translocations, 18 gains 13 and mutations involving BCL-6.…”

Section: Introductionmentioning

confidence: 99%

A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma

et al. 2005

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The role of TP53 mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre-and post-transformation. The entire TP53 coding sequence was screened and immunocytochemistry performed to determine expression of p53 and its key regulator MDM2. A total of 10 mutations were detected in eight patients (28%), although none were present at FL diagnosis. Mutations were not detected solely at the time of transformation; in three patients, mutated TP53 arose in at least one antecedent FL sample (6 months, 2.5 years and 4 years prior to transformation). Loss of heterozygosity at the TP53 locus occurred in 2/20 informative patients (only in t-FL samples). p53 staining was positive in 82% (9/11) of available biopsies with a missense mutation, and negative in 71% (45/63) with wtTP53. MDM2 expression was significantly higher in t-FL samples (mean 72% positive; 95% confidence interval (95% CI) 68-76%) than FL (mean 58% positive; 95% CI 54-62%) (Po0.001) but did not correlate with TP53 status. TP53 mutation has only a limited role in the transformation of FL, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent and may provide a more rational therapeutic target.

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High-dose therapy with autologous haematopoietic support in patients with transformed follicular lymphoma: A study of 27 patients from a single centre

Abstract: It is appropriate to consider HDT for younger patients with FL-t in remission. Repeat biopsy should be considered for patients with recurrent disease. There is a risk of late MDS in patients undergoing this treatment.

Cited by 77 publications

References 23 publications

Long-term event-free survivors after high-dose therapy and autologous stem-cell transplantation for low-grade follicular lymphoma

Long-term event-free survivors after high-dose therapy and autologous stem-cell transplantation for low-grade follicular lymphoma

Transformed lymphoma: an Achilles' heel of non-Hodgkin's lymphoma

A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma

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