High-dose chemotherapy and autologous hematopoietic stem-cell transplantation for aggressive non-Hodgkin's lymphoma.

Summary:characteristics. and high-grade lymphomas, high-dose chemotherapy (HDC) with autologous stem cell rescue (SCR) provides adults (ages 18-60 years; median 36) underwent alloBMT for lymphoma after failure of standard chemolong-term disease-free survival in 40-60% of patients who relapse with chemotherapy-sensitive disease, and has been therapy. Twenty-one had NHL and six had HD (nodular sclerosis). Thirteen patients had primary refractory disshown to be superior to conventional salvage chemotherapy alone. 2 Long-term survival for patients with primary refracease or chemotherapy-resistant relapses; two of these had relapsed after autoBMT. Three patients had tory or chemotherapy-resistant disease treated with HDC and autologous SCR, however, is only about 10%. 3 untested relapses (one of them had relapsed after autoBMT), and 11 had chemotherapy-sensitive relapses.Low-grade lymphomas are indolent disorders with a high rate of response to initial treatment and a median survival Twenty-four received HLA-matched bone marrow from a sibling (one twin); three received haploidentical marduration of 7-9 years. 3 Although aggressive chemotherapy regimens including HDC and autologous SCR in this group row cells. Nine (33%) died from lymphoma. Eleven (41%) died of treatment-related causes. Opportunistic of patients have shown progression-free survival rates of 50%, follow-up has been relatively short. 4,5 Again, patients infections were a substantial problem leading to eight of these deaths (30%). Six patients (22%) survive free with advanced, recurrent or refractory disease have had a very poor prognosis. of lymphoma 17-70 months post-BMT (median, 56 months); four had had sensitive relapses, one had had Several groups have begun examining the role of allogeneic bone marrow transplantation (alloBMT) for those a resistant relapse, and one had had nontested relapse. Three have chronic GVHD (limited in one; extensive in HD/NHL patients who are younger than 60 years of age and have a suitable HLA (human leukocyte antigen) comtwo). One HD patient who had relapsed after autoBMT remains in remission 19 months after alloBMT. No patible donor. Advantages of alloBMT include hematopoietic rescue with tumor-free marrow, the potential for a therapy-related myelodysplasia has been observed. We conclude that alloBMT has substantial morbidity in graft-versus-lymphoma effect leading to a lower incidence of relapse post-transplantation, and lower rates of therapyheavily pretreated lymphoma patients due to acute toxicity, infections and GVHD. However, 22% of our related leukemia. The few studies that have been performed using alloBMT have reported a 25-35% early mortality HD/NHL patients have had long-term disease-free survival.rate, with deaths secondary to graft-versus-host disease (GVHD), as well as regimen-related toxicities and infecKeywords: allogeneic marrow transplantation; Hodgkin's; lymphoma tion. 6 However, lower than expected relapse rates have been observed in surviving patients, thus suggesting the possibility of an immune-...

Section: Discussionmentioning

confidence: 51%

Allogeneic bone marrow transplantation for relapsed and refractory Hodgkin’s disease and non-Hodgkin’s lymphoma

Daugherty

Larson

1997

“…[1][2][3][4][5] However, in contrast to autologous or allogeneic BMT, little information is available concerning the reconstitution of the immune system following autologous peripheral blood stem cell transplantation (PBSCT). As after BMT, the CD4/CD8 ratio seems to be inversed after PBSCT, but lymphocyte subpopulations and functions recover more rapidly, including the proliferative response to mitogens and the cytotoxic activity of lymphocytes after stimulation with high-dose IL-2 (lymphocyte-activated killer cells, LAK).…”

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confidence: 99%

Assessment and characterization of the cytolytic T lymphocyte response against Epstein–Barr virus in patients with non-Hodgkin’s lymphoma after autologous peripheral blood stem cell transplantation

Nolte

Buhmann

Straka

et al. 1998

Summary:The cytolytic T lymphocyte (CTL) response has often been used to assess the reconstitution of T cell function after allogeneic or autologous bone marrow transplantation (BMT). Less is known, however, about the reconstitution of the CTL response after peripheral blood stem cell transplantation (PBSCT). Therefore, we investigated the CTL response against Epstein-Barr virus (EBV) of patients undergoing autologous PBSCT. CTLs of six patients with relapsed non-Hodgkin's lymphoma and multiple myeloma were established before and at different times after PBSCT by in vitro stimulation of peripheral blood lymphocytes with autologous EBVtransformed lymphoblastoid cell lines (LCLs). The efficiency of T cell priming by LCLs was assessed at the time of initiation of CTL lines; the proliferative response was strongly reduced during the first 4 months and increased 5 months or more following PBSCT. Cytolytic activity was measured after three or four restimulations of CTLs. All patients investigated had a detectable EBV-specific CTL response which was poor during the first weeks after transplantation, accompanied by a strong non-MHC-restricted cytotoxic activity and a high proportion of CD56-positive T cells. Five or more months after PBSCT, a specific CTL response against EBV was seen which was similar to the situation prior to PBSCT, while the unspecific cytotoxic response decreased. Blocking experiments with monoclonal anti-CD3, anti-CD8 or anti-MHC I antibodies resulted in substantial inhibition of autologous LCL lysis, whereas anti-CD4 or anti-MHC II antibodies had no effect. Finally, autologous PHA blasts of a patient with the HLA haplotype A1/9+, B5/8+, Cw4/7+, were loaded with various EBNA-derived nonapeptides known to be presented by HLA B8 or A11, and exposed to autologous, EBV-directed In the last few years, autologous peripheral blood stem cell transplantation (PBSCT) has been established as a standard treatment for relapsed aggressive non-Hodgkin's lymphoma and has proven advantageous when compared with autologous or allogeneic bone marrow transplantation (BMT). 1-5 However, in contrast to autologous or allogeneic BMT, little information is available concerning the reconstitution of the immune system following autologous peripheral blood stem cell transplantation (PBSCT). As after BMT, the CD4/CD8 ratio seems to be inversed after PBSCT, but lymphocyte subpopulations and functions recover more rapidly, including the proliferative response to mitogens and the cytotoxic activity of lymphocytes after stimulation with high-dose IL-2 (lymphocyte-activated killer cells, LAK). [6][7][8][9][10] Previous investigations mainly examined non-specific lymphocyte functions in patients undergoing autologous PBSCT and the reconstitution of the antigen-specific cytolytic T lymphocyte (CTL) response has not been evaluated so far. Therefore, we examined the CTL response of these patients to Epstein-Barr virus (EBV), a widespread lymphotropic herpes virus. Most people are infected with EBV by adulthood, and the life-long persist...

“…The initial chemosensitivity to salvage chemotherapy remained the most important prognostic factor. [10][11][12] The proportion of patients salvaged by HDT ϩ ASCT reached 45-60% in patients with good prognostic features according to the prognostic model proposed by Vose et al 13 for NHL patients and by Brice et al 14 for those with HD. However, for patients with adverse prognostic factors, the probability of being cured decreases rapidly to under 40% with standard conditioning regimen and ASCT.…”

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confidence: 99%

Tandem transplant of peripheral blood stem cells for patients with poor-prognosis Hodgkins’s disease or non-Hodgkin’s lymphoma

Fitoussi

Simon

Brice

et al. 1999

Summary:To improve the results of high-dose therapy with autologous stem cell transplantation, new conditioning regimens with acceptable toxicity must be developed. The aim of this study was to evaluate the feasibility and toxicity of two myeloablative regimens performed at a 2-month interval. After salvage chemotherapy and collection of peripheral stem cell progenitors (median CD34 ؉ cells/kg: 11 ؋ 10 6 /kg), (n ‫؍‬ 15) patients with aggressive non-Hodgkin's lymphoma with poor prognostic factors or refractory Hodgkin's disease (n ‫؍‬ 9) received intensified regimens. The first conditioning regimen, consisting of BCNU-cyclophosphamide-VP16-mitoxantrone was followed by transplantation of a median number of 4 ؋ 10 6 CD34 ؉ cells/kg; then, after a median interval of 56 days, a second preparative regimen, combining busulfan-aracytine-melphalan or TBI ؉ aracytine-melphalan, was followed by transplantation of a median of 4 ؋ 10 6 CD34 ؉ cells/kg. After regimens 1 and 2, respectively: median time to neutrophil recovery Ͼ500/ l was 11 days (both times); median time to platelet counts Ͼ50 000/ l was 14 and 36 days, but values Ͼ20 000/ l were reached by days 13 and 16 (P ‫؍‬ 0.9); mucositis grade III-IV was observed in 11 and 15 cases. The median number of days with fever Ͼ38؇C was significantly higher (7.8 days) after the second transplant (P Ͻ0.05). Three cases of veno-occlusive disease (VOD) were observed after the second transplant. At a median follow-up of 18 months, 14/24 (58%) patients remained in CR, seven patients had died (two of VOD and five after relapse) and two were alive in relapse. These results indicate that tandem transplants performed at a 2-month interval in poor risk lymphoma can be used with acceptable hematotoxicity. VOD remains the major drawback and hepatotoxic drugs, such as busulfan, should be used with caution. Longer term followup of a larger cohort of patients is needed to ascertain the overall efficacy. Keywords: tandem transplants; Hodgkin's disease; nonHodgkin's lymphoma; veno-occlusive disease Conventional-dose anthracycline-containing chemotherapy associated with radiotherapy has now been well documented to result in long-term disease-free survival in 60-70% of the patients with advanced Hodgkin's disease (HD) 1 and 45-50% of those with unselected aggressive non-Hodgkin's lymphoma (NHL). 2 For NHL patients, prognosis is determined based on the clinical characteristics defined by the International Prognostic Index (IPI), 3 with the survival rate for patients with 0-2 adverse factors ranging from 80 to 60%. However, for patients with Ͼ2 adverse prognostic factors actuarial survival is inferior to 40% and for those with primary refractory disease who fail to achieve complete remission (CR) after standard chemotherapy, the prognosis is poor with conventional salvage chemotherapy. 4 The most promising approach for these very poorrisk patients is the use of high-dose therapy (HDT) followed by autologous stem cell transplant (ASCT). Prospective trials have shown HDT ϩ ASCT to be superior to che...