Long-term clinical and molecular remission after allogeneic stem cell transplantation (SCT) in patients with poor prognosis non-Hodgkin's lymphoma

Abstract

From 1987 to 1999 35 patients with poor prognosis non-Hodgkin's lymphoma (NHL) underwent allogeneic stem cell transplantation (SCT) at the University Hospitals of Vienna and Graz. Initial biopsy specimens were reclassified according to the Revised European-American Classification of Lymphoid Neoplasms (REAL). All patients surviving 28 days engrafted. Twenty-eight of them (93%) attained clinical remission. At the last follow-up 14 patients were alive and disease-free at a median of 5.0 (range, 2.3-12.9) years after allogeneic SCT. The actuarial overall survival is 35%. Five patients relapsed 1.8 to 27.6 months after transplant, the probability of relapse is 23%. Of the 21 deaths following SCT, seven were due to relapse/refractory disease and 14 due to transplant-related causes. The probability of treatment-related mortality is 48%. After SCT, minimal residual disease (MRD) was monitored by polymerase chain reaction (PCR) in seven patients with a BCL-2/IgH translocation and in 13 with a clonal immunoglobulin heavy chain (IgH) rearrangement. All 20 patients attained clinical remission rapidly and converted to PCR negativity. In the follow-up nine of these patients are in long-term clinical and molecular remission, six PCR-negative patients died of transplant-related causes and five patients relapsed. In summary, allogeneic stem cell transplantation has a curative potential for patients with refractory and recurrent non-Hodgkin's lymphoma. In our series long-term disease-free survival was associated with molecular disease eradication after SCT. Treatmentrelated mortality rate was high, thus earlier referral of selected patients to allogeneic SCT should be considered. Leukemia (2001) 15, 635-641.

High-dose cyclophosphamide, BCNU, and VP-16 (CBV) conditioning before allogeneic stem cell transplantation for patients with non-Hodgkin's lymphoma

“…29,30 Although there are no available randomized data to show superiority of an allogeneic approach in NHL, the advantage of tumor-free stem cells and a graft-versus-lymphoma effect make this an attractive alternative for young patients with a history of heavy pretreatment or refractory lymphoma. 3,14,31,32 A graft-versus-lymphoma effect may overcome chemotherapy resistance and allow long-term survival in a minority of refractory lymphoma patients. 33 Unfortunately , improvements in relapse-free survival after allogeneic SCT are generally offset by increased treatment-related mortality.…”

“…15,33,44 This indicates that CBV is sufficiently immunosuppressive to allow engraftment of donor hematopoietic cells. Other investigators have shown that CBV permits allogeneic stem cell engraftment in lymphoma patients with prior doselimiting radiation therapy.…”

Why aren't we performing more allografts for aggressive non-Hodgkin's lymphoma?

“…Relapse is also not consistently decreased in the presence of GVHD 19,[20][21][22][23][24][25] (Table 2) nor increased after transplantation with T-cell-depleted marrow. [26][27][28] Isolated but impressive cases of response to withdrawal of immunosuppression and to donor leukocyte infusions have also been reported in some, 19,29,30 but not most cases.…”

“…[19][20][21][22][23][24][25]27,38,44,45 Those refractory to salvage chemotherapy at the time of transplant generally have eventfree survival less than 25%, and in some cases no event-free survival 20,22 because of both increased rates of relapse and increased transplant-related mortality. This pattern is not dissimilar to that seen with autoSCT, suggesting that there is only a limited role for alloSCT to overcome chemoresistance.…”

Increase in Minimal Residual Disease in Peripheral Blood before Clinical Relapse in Dogs with Lymphoma that Achieved Complete Remission after Chemotherapy

“…9,10 Monitoring MRD is an essential tool for risk group stratification and appears to be useful for predicting relapse in some hematopoietic and lymphoid malignancies of humans. 10,[11][12][13] In addition, several reports document the usefulness of MRD to provide a molecular assessment of treatment efficacy for diffuse large B-cell lymphoma (DLBCL) in humans, [14][15][16] which is the disease to which high-grade B-cell lymphoma in dogs has been compared. We previously reported a highly sensitive MRD detection system in canine lymphoma by a real-time PCR that enabled detection of 1 tumor cell per 10 4 peripheral blood mononuclear cells (PBMCs).…”