Matched-Cohort Analysis of Autologous Hematopoietic Cell Transplantation with Radioimmunotherapy versus Total Body Irradiation–Based Conditioning for Poor-Risk Diffuse Large Cell Lymphoma

We conducted a matched-cohort analysis of autologous transplant conditioning regimens for diffuse large cell lymphoma in 92 patients treated with either radioimmunotherapy (RIT) or total body irradiation (TBI)–based conditioning regimens. The RIT regimen consisted of 0.4 mCi/kg of 90Y-ibritumomab tiuxetan plus BEAM (BCNU, etoposide, cytarabine, melphalan). The TBI-based regimen combined fractionated TBI at 1200 cGy, with etoposide and cyclophosphamide. Five factors were matched between 46 patient pairs: age at transplant ±5 years, disease status at salvage, number of prior regimens, year of diagnosis ±5 years, and year of transplantation ±5 years. Patients in the TBI group had higher rates of cardiac toxicity and mucositis, whereas Z-BEAM patients had a higher incidence of pulmonary toxicity. Overall survival at 4 years was 81.0% for the Z-BEAM and 52.7% for the TBI group (P = .01). The 4-year cumulative incidence of relapse/progression was 40.4% and 42.1% for Z-BEAM and TBI, respectively (P = .63). Nonrelapse mortality was superior in the Z-BEAM group: 0% compared with 15.8% for TBI at 4 years (P < .01). Our data demonstrate that RIT-based conditioning had a similar relapse incidence to TBI, with lower toxicity, resulting in improved overall survival, particularly in patients with ≥2 prior regimens

High-Dose Therapy and Autologous Hematopoietic Cell Transplantation in Peripheral T Cell Lymphoma (PTCL): Analysis of Prognostic Factors

Patients with peripheral T cell lymphoma (PTCL) have a poor prognosis with current treatment approaches. We examined the outcomes of high-dose therapy (HDT) and autologous hematopoietic cell transplant (AHCT) on the treatment of PTCL and the impact of patient/disease features on long-term outcome. Sixty-seven patients with PTCL–not otherwise specified (n = 30), anaplastic large cell lymphoma (n = 30), and angioimmunoblastic T cell lymphoma (n = 7) underwent HDT/AHCT at the City of Hope. The median age was 48 years (range: 5-78). Twelve were transplanted in first complete remission (1CR)/partial remission (PR) and 55 with relapsed or induction failure disease (RL/IF). With a median follow-up for surviving patients of 65.8 months (range: 24.5-216.0) the 5-year overall survival (OS) and progression-free survival (PFS) were 54% and 40%, respectively. The 5-year PFS was 75% for 1CR/PR compared to 32% for RL/IF patients (P = .01). When the Prognostic Index for PTCL unspecified (PIT) was applied at the time of transplant, patients in the PIT 3-4 group had 5-year PFS of only 8%. These results show that HDT/AHCT can improve long-term disease control in relapsed/refractory PTCL and that HDT/AHCT should ideally be applied either during 1CR/PR, or as part of upfront treatment. More effective and novel therapies are needed for patients with high-risk disease (PIT 3-4 factors) and allogeneic HCT should be explored in these patients

Transformed non‐Hodgkin lymphoma in the rituximab era: analysis of the NCCN outcomes database

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100290/1/bjh12570.pd

Reduced-Intensity Conditioning with Fludarabine, Cyclophosphamide, and High-Dose Rituximab for Allogeneic Hematopoietic Cell Transplantation for Follicular Lymphoma: A Phase Two Multicenter Trial from the Blood and Marrow Transplant Clinical Trials Network

Allogeneic hematopoietic cell transplantation (alloHCT) can induce long term remissions in chemosensitive relapsed follicular lymphoma (FL). The BMT CTN conducted a multicenter phase 2 trial to examine the efficacy of alloHCT using reduced intensity conditioning (RIC) with rituximab (RTX) in multiply relapsed, chemosensitive FL. The primary endpoint was 2 year progression-free survival (PFS). The conditioning regimen consisted of fludarabine, cyclophosphamide and high-dose RTX (FCR) in which 3 of the 4 doses of RTX were administered at a dose of 1 gm/m2. Graft vs host disease (GvHD) prophylaxis was with tacrolimus and methotrexate. Sixty five patients were enrolled and 62 were evaluable. Median age was 55 years (range, 29-74). This group was heavily pre-treated: 77% had received ≥ 3 prior regimens, 32% had received ≥ 5 prior regimens and 11% had received prior autologous HCT. Donors were HLA-matched siblings (n=33) or HLA-matched unrelated adults (n=29). No graft failures occurred. The overall response rate after HCT was 94% with 90% in complete remission (CR), including 24 patients not in CR before alloHCT. With a median follow-up of 47 months (range, 30-73), 3 year PFS and overall survival rates were 71% (95% confidence interval: 58%-81%) and 82% (70%-90%) respectively. Three year cumulative incidences of relapse/progression and non-relapse mortality were 13% and 16%, respectively. Two year cumulative incidences of grade 2-4 and grade 3-4 acute GvHD were 27% and 10%, respectively and extensive chronic GvHD incidence was 55%. Serum RTX concentrations peaked at day +28 and remained detectable as late as 1 year in 59% of patients with available data. In conclusion, alloHCT with FCR conditioning confers high CR rates, a low incidence of relapse/progression and excellent survival probabilities in heavily pretreated FL patients

Remission of refractory Sezary syndrome after bone marrow transplantation from a matched unrelated donor

AbstractSezary syndrome is a leukemic variant of mycosis fungoides (MF)/cutaneous T-cell lymphoma (CTCL). Bone marrow transplantation (BMT) from a matched unrelated donor was performed in a 22-year-old woman with a 10-year history of Sezary syndrome who had failed treatment with corticosteroids, methotrexate, photochemotherapy, photopheresis, hydroxyurea, interferon-alpha, and cladarabine. At the time of BMT, she had persistent erythrodermic skin disease, adenopathy, circulating Sezary cells and bone marrow (BM) involvement. The patient underwent BMT from a 6/6 HLA-matched unrelated male donor in August 1996. A BM biopsy obtained on day 30 after BMT showed no evidence of lymphoma and complete male donor engraftment. Her skin lesions resolved within 100 days after transplant. Complete staging studies, including T-cell receptor gene rearrangement studies performed at 36 months post-BMT, showed no evidence of recurrent Sezary syndrome. This represents her first durable remission since the initial diagnosis more than 12 years ago. To our knowledge, this is the first patient with refractory Sezary syndrome who has been successfully treated with allogeneic unrelated donor BMT. Our results indicate that this modality may be effective in inducing remission in refractory MF/CTCL, including Sezary syndrome.Biol Blood Marrow Transplant 1999;5(6):400-4