Lack of correlation between numbers of circulating t(14;18)-positive cells and response to first-line treatment in follicular lymphoma

Mandigers, Caroline; Meijerink, Jules P.P.; Mensink, E. J. B. M.; Tönnissen, Evelyn; Hebeda, Konnie M.; Bogman, M.J.J.T.; Raemaekers, John

doi:10.1182/blood.v98.4.940

Cited by 60 publications

(37 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…If it would be possible to predict disease control after first-line therapy, these therapies could be selected for patients with a high likelihood of early relapse. With qualitative PCR, several studies were able to document a relationship between molecular response and time to relapse in patients treated with standard-dose chemotherapy [4,5,26], with high-dose chemotherapy [7,[27][28][29][30] and with rituximab-containing regimen [8,31,32]. Due to the low number of patients and the limited follow-up time of 6 months, we can only speculate on the role of molecular diagnostics for the prediction of relapsed disease.…”

Section: Discussionmentioning

confidence: 99%

Commercial LightCycler®-based quantitative real-time PCR compared to nested PCR for monitoring of Bcl-2/IgH rearrangement in patients with follicular lymphoma

Kornacker

Schmitt

et al. 2008

Ann Hematol

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Commercial LightCycler®-based quantitative real-time PCR compared to nested PCR for monitoring of Bcl-2/IgH rearrangement in patients with follicular lymphoma

Kornacker

Schmitt

et al. 2008

Ann Hematol

View full text Add to dashboard Cite

“…In available bone marrow and blood samples, lymphoma cells were analysed by real-time quantitative polymerase chain reaction (PCR) of t(14;18)-positive cells in follicular NHL, 21,22 and by immunophenotyping in small lymphocytic NHL. The sensitivity of the PCR is detecting a single lymphoma cell in 75 000 normal cells.…”

Section: Methodsmentioning

confidence: 99%

Graft-versus-lymphoma effect of donor lymphocyte infusion in indolent lymphomas relapsed after allogeneic stem cell transplantation

Mandigers

Verdonck

Meijerink

et al. 2003

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:Donor lymphocyte infusions (DLI) are used to treat relapsed haematological diseases after allogeneic stem cell transplantation (SCT). We treated seven patients with DLI for indolent non-Hodgkin's lymphoma relapsed after SCT. In available blood and bone marrow samples, lymphoma cells were analysed by real-time quantitative polymerase chain reaction of t(14;18)-positive cells in follicular lymphoma, and by immunophenotyping in small lymphocytic lymphoma. Before DLI, three patients were treated with chemo-and/or radiotherapy, and one with rituximab. Evaluable responses to pre-DLI therapy were stable disease in one and partial remission (PR) in two patients. Six patients responded to DLI (complete remission (CR) in four and PR in two). After DLI, acute graft-versus-host disease (GVHD) occurred in 3/6 patients, classified as grade 2, whereas only limited chronic GVHD was seen (n ¼ 5). The four continuous CR are lasting for median 65 þ (43-89) months. In the remaining patient, not responding to DLI, progressive disease was seen later on; chemotherapy followed by another DLI resulted in CR. In three cases, clinical responses to DLI could be substantiated by molecular or immunophenotypic analysis of lymphoma cells. We conclude that DLI is effective for treatment of indolent lymphoma relapsing after SCT. Myeloablative therapy followed by allogeneic stem cell transplantation (SCT) has emerged as a promising treatment modality for selected patients with indolent types of non-Hodgkin's lymphoma (NHL). Response rates of 50-70% and relapse percentages of about 15 have been reported in series of predominantly heavily pretreated patients. 1-3 As similar conditioning regimens followed by autologous stem cell rescue result in comparable response, but higher relapse rates, 1,4,5 a graft-versus-lymphoma effect is assumed to be involved in allogeneic SCT, as already suggested over a decade ago. 6 In case of relapsed haematologic disease after allogeneic SCT, remission can still be induced by shifting the balance between patient and donor immunoreactive cells in favour of the donor, either by diminishing the patient's immunosuppressive medication, 7 or by infusion of lymphocytes derived from the original stem cell donor. [8][9][10][11][12][13][14][15] Especially in relapsed chronic myeloid leukaemia after allogeneic transplantation, these donor lymphocyte infusions (DLI) are effective, whereas in relapsed acute leukaemia responses to DLI are rather disappointing.Earlier, we described a patient with relapsed follicular NHL after allogeneic SCT, in whom the clinically observed graft-versus-lymphoma effect of DLI was substantiated by molecular analysis of circulating cells carrying the characteristic chromosomal translocation t(4;18). 16 Here, we describe seven patients treated with DLI for indolent lymphoma relapsed after allogeneic SCT. The observed responses are illustrated with available molecular and immunophenotypic data. Patients and methods PatientsSince 1989, in the University Medical Centers Nijmegen and Utrecht, 50 pa...

show abstract

“…33 Similar findings suggesting that PCR is not predictive of outcome in the setting of biologic therapy have been observed in a group of patients with follicular lymphoma treated with standard chemotherapy and interferon. 8 This observation has important implications in interpreting molecular response following ASCT. Preliminary results of trials utilizing rituximab as in vivo purging prior to ASCT have suggested high molecular response rates.…”

Section: Discussionmentioning

confidence: 99%

“…5 Patients who achieve 'molecular response' (PCR negativity for bcl-2) after certain treatments for follicular lymphoma appear to have prolonged disease-free survival (DFS), although this is controversial and the subject of ongoing research. [6][7][8] High-dose chemotherapy or chemoradiotherapy followed by autologous stem cell transplantation (ASCT) results in prolonged DFS in a substantial subset of patients with follicular NHL that has progressed after chemotherapy. [9][10][11][12] When bone marrow is used as a source of stem cells for ASCT, the detection of lymphoma cells by PCR is a highly significant predictor of subsequent relapse.…”

mentioning

confidence: 99%

Ex vivo B cell depletion using the Eligix B Cell SC system and autologous peripheral blood stem cell transplantation in patients with follicular non-Hodgkin's lymphoma

Friedberg

Kim

et al. 2003

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:One limitation of ASCT is the potential reinfusion of tumor cells contaminating PBSC. The Eligix B cell SC system consists of high-density microparticles coated with anti-B cell antibodies. To determine if this system eliminates B cells and lymphoma cells from PBSC, immunocytochemistry and PCR of the bcl-2/IgH rearrangement were performed, and correlated with patient outcome after ASCT. Eligible patients (n ¼ 29) had relapsed or transformed follicular NHL with bone marrow involvement o20%, and all lymph nodes o5 cm. PBSCs were mobilized with cyclophosphamide/G-CSF (n ¼ 21), and patients were conditioned with cyclophosphamide, carmustine and etoposide.Using immunocytochemistry on PBSC, the median number of CD20+ cells pre-purge was 310/10 6 (range 0-16692) and post-purge was 0.75/10 6 ; the median log B cell depletion was 2.7 (range 1.4-3.9). B cell depletion correlated with PFS after ASCT (P ¼ 0.06). Of 17 available samples for PCR, only four had a detectable t(14;18) breakpoint. After purging, all four remained PCR+; two had a 1-3 log depletion of lymphoma cells. At median follow-up of 18 months, 10 patients, including five infused with PCR-negative PBSC, have had disease progression. The paucity of PCR-informative patients, possibly related to in vivo rituximab therapy, limited the utility of minimal residual disease as a surrogate marker of clinical outcome.

show abstract

Lack of correlation between numbers of circulating t(14;18)-positive cells and response to first-line treatment in follicular lymphoma

Cited by 60 publications

References 19 publications

Commercial LightCycler®-based quantitative real-time PCR compared to nested PCR for monitoring of Bcl-2/IgH rearrangement in patients with follicular lymphoma

Commercial LightCycler®-based quantitative real-time PCR compared to nested PCR for monitoring of Bcl-2/IgH rearrangement in patients with follicular lymphoma

Graft-versus-lymphoma effect of donor lymphocyte infusion in indolent lymphomas relapsed after allogeneic stem cell transplantation

Ex vivo B cell depletion using the Eligix B Cell SC system and autologous peripheral blood stem cell transplantation in patients with follicular non-Hodgkin's lymphoma

Contact Info

Product

Resources

About