The implication of follicular lymphoma patients receiving allogeneic stem cell transplantation from donors carrying t(14;18)-positive cells

Abstract

Summary:We performed real-time quantitative polymerase chain reaction (RQ-PCR) in peripheral blood (PB) and/or bone marrow (BM) samples collected pre-and post transplant from 23 recipient-donor pairs receiving allogeneic stem cell transplantation (allo-SCT) for follicular lymphoma (FL). Of 23 donors, 11 had a PB and/or BM sample positive for t(14;18) (BCL2/IGH fusion) at low levels (oone t(14;18) cell in 10K total cells). Recipients from donors with (n ¼ 11) and those without (n ¼ 12) detectable t(14:18) cells were similar in age, sex, and disease status pretransplant. No differences in the incidence of graft-versus-host-disease (GVHD), delayed engraftment, relapse rate, disease-free survival and overall survival were identified between the groups. Two recipients without detectable t(14;18) cells pretransplant showed detectable t(14;18) cells at 2 and 11 years after receiving grafts from donors with t(14:18) cells. Neither patient developed FL 1.5 and 2 years after the emergence of t(14;18) cells. Although the sample size is relatively small, our findings suggest that individuals carrying t(14;18) cells may not be excluded as donors given the lack of an association of t(14;18) detected in donors with adverse clinical outcome. It may be necessary to screen for the donor's t(14;18) status before using t(14;18) for monitoring minimal residual disease by RQ-PCR to exclude the possibility of confounding donor's t (14;18) [4][5][6][7][8][9][10][11] Allogeneic stem cell transplantation (allo-SCT) is of increasing interest as a therapeutic option for patients due to the potential of a graft-versus-lymphoma effect to provide long-term disease control. [12][13][14][15] We have recently reported that monitoring the tumor load of t(14;18) cells by real-time quantitative PCR (RQ-PCR) may predict the outcome of FL patients after allo-SCT. 16 Patients with tumor loads of greater than one t(14;18) cell per 10K total cells post transplantation have a higher risk of clinical relapse than those without. The monitoring of minimal residual disease (MRD) by RQ-PCR allows for the development of strategies, such as donor lymphocyte infusions to be employed at a stage of molecular relapse in patients whose RQ-PCR results suggest a high likelihood of subsequent clinical relapse.The utility of using RQ-PCR to monitor tumor load or MRD after allo-SCT, however, can be confounded by the presence of t(14;18) cells of donor origin. We recently described the disappearance of a patient's t(14;18) clone early post transplant with the concomitant emergence and long-term persistence of the donor's t(14;18) clone without development of FL. 17 Although it has not been well studied, donor carrying t(14;18) clones detectable by RQ-PCR could theoretically develop into FL in an immunosuppressed recipient who may have a genetic susceptibility to develop FL. In addition, the presence of t(14;18) clones in the donor could serve as a surrogate marker of a stem cell defect and thus affect transplant outcome in some other manner. Thus, the aims of the current ...

Presence of t(14;18) positive cells in blood and bone marrow does not predict outcome in follicular lymphoma

“…A study of allogeneic stem cell transplantation in follicular lymphoma reported similar outcome (DFS and OS) in recipients of stem cells from donors who had or had not t(14;18) detectable in peripheral blood or bone marrow [27].…”

Molecular genetic analysis of haematological malignancies II: mature lymphoid neoplasms

“…For post‐allograft patients, there is no clear data on the prognostic role for MRD monitoring. However, as BCL2 ‐ IGH rearrangements can be detected at low level within normal individuals, a significant number of allogeneic donor grafts will contain small numbers of BCL2‐IGH positive cells (McGregor et al. , 2005).…”

“…, 2005). Despite this, patients transfused with grafts from BCL2 ‐ IGH positive donors do not perform less well in terms of risk of relapse, survival and transplant‐related morbidity (McGregor et al. , 2005) even though breakpoints in normal individuals appear to be the same as those detected in patients (Roulland et al.…”

Bone Marrow and Peripheral Blood Stem Cell Transplantation

“…Few comparative trials have been performed, and hence little evidence exists that any one combination regimen is superior to another. 322,323 Allogenic HSCT continues to be investigated to improve outcomes. Some entities remain localized, such as the nasal T/ NK cell lymphoma, requiring only CHOP-like chemotherapy followed by involved field radiotherapy (IFRT) and are generally associated with good prognosis.…”