Primary extranodal CD30-positive T-cell non-Hodgkin's lymphoma of the oral mucosa

Abstract Denileukin diftitox (Ontak) is a fusion protein combining the enzymatically active domain of diphtheria toxin and the full-length sequence of interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor (IL-2R). The drug has established efficacy in cutaneous T-cell lymphoma (CTCL), and we have recently demonstrated its single-agent activity in B-cell non Hodgkin’s lymphoma (NHL) (Dang et al. Journal of Clinical Oncology. In Press). We initiated a phase II study to evaluate its efficacy in relapsed/refractory T-cell NHL, excluding CTCL. Denileukin diftitox was administered at a dose schedule of 18 μg/kg/day by IV infusion once daily for 5 days every three weeks, for up to 8 cycles. Premedications in the form of corticosteroids, antihistamines and fluids were given prior to each drug infusion to reduce the incidence and severity of acute hypersensitivity. 14 patients are currently evaluable for response. Median age was 57 (range 26–80), and mean number of previous treatments was 2.2 (range 1–4). Tumor CD25 status was determined by immunohistochemistry and/or flow cytometry, with CD25-positivity being defined as 10% or more of tumor cells expressing detectable CD25. Of the 7 patients with CD25+ T-NHL, there were 2 CR (1 case of Alk-1 negative ALCL and 1 case of PTCL), 3 PR (1 case of PTCL and 2 cases of angioimmunoblastic lymphoma), 1 SD (1 case of PTCL) and 1 PD (1 case of PTCL). Of the 7 patients with CD25− T-NHL, there were 2 PR (1 case of PTCL and 1 case of T/NK-lymphoma), 4 SD (3 cases of PTCL and 1 case of Sezary syndrome), and 1 PD (1 case of angioimmunoblastic lymphoma). Overall response rate (CR+ PR) was 50%, with 2 of 14 patients having CR (14%) and 5 of 14 patients having PR (36%). One patient with Alk-1negative ALCL still has an ongoing CR at 15+ months. Treatment was well-tolerated, with the majority of toxicity being grade 1 or 2 and transient. Denileukin diftitox appears to have activity in relapsed/refractory T-cell NHL, and is well-tolerated at the dosing schedule tested. Additional patients are being studied to further evaluate the relationship between detectable CD25 expression and tumor response to denileukin diftitox.

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Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) for Patients with Refractory or Relapsed Non-Hodgkin’s Lymphoma (NHL).

Blood ◽

10.1182/blood.v108.11.5356.5356 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5356-5356

Author(s):

Hugues de Lavallade ◽

Reda Bouabdallah ◽

Catherine Faucher ◽

Sabine Furst ◽

Jean El-Cheikh ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Cumulative Incidence ◽

Hodgkin’S Lymphoma ◽

Hodgkin's Lymphoma ◽

Cell Group ◽

High Grade ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma

Abstract This study aimed to evaluate the role of RIC allo-SCT for relapsed or refractory non-Hodgkin’s lymphoma (NHL). We report here our experience in 25 consecutive patients transplanted in a single center for high grade (n=17) or follicular NHL (FL; n=8). In the high grade NHL group, median age was 46 (range, 24–63) years, and all 17 patients received 2 or more previous chemotherapy regimens prior to RIC allo-SCT. In addition, 12 patients (71%) had failed autologous SCT and 6 patients (35%) had chemoresistant disease at time of allo-SCT. Among the 8 patients transplanted for a heavily pretreated follicular NHL (FL), median age was 52 (range, 34–59) years and median number of prior lines of therapy was 3 (range, 2–5), with 3 patients (38%) having chemoresistant diseases and 4 patients (50%) relapsing after autologous SCT. Among the 17 patients with aggressive high grade NHL, we compared the outcome of T-cell and B-cell aggressive NHL. With a median follow-up of 15.4 (range, 3.4-65.2) months, the cumulative incidence of non-relapse mortality was 6%, (95%CI, 0.3%-31%) and the Kaplan-Meier estimate of progression-free survival (PFS) was significantly higher in the T-cell as compared to the B-cell group (P= 0.03; 100% vs. 40% at 3 years). In the FL group, the cumulative incidence of non-relapse mortality was 25% (95%CI, 3%–65%). Six patients (75%) showed objective disease response with complete remission (CR) occurring concomitantly to graft-versus-host disease, including one CR after donor lymphocytes infusion. With a median follow-up of 19 (range, 7–85) months, 6 patients from the FL group are still alive of whom 5 in CR. We conclude that a potent graft-vs.-lymphoma (GVL) may be achieved in FL patients, even those with chemoresistant disease or who have relapsed after autologous SCT. In the high grade NHL group, strategies aiming to enhance the GVL effect (Rituximab-based RIC and/or Rituximab maintenance therapy) in the B cell subtype are still needed. However, RIC allo-SCT is a feasible and promising strategy for aggressive NHL, with particularly low toxicity, and T-cell aggressive NHL benefiting most from a potent GVL effect, likely overcoming the poor prognosis usually associated with this phenotype.

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T- Cell Non-Hodgkin's Lymphoma, Data From a Mexican Tertiary Health Center..

Blood ◽

10.1182/blood.v114.22.5030.5030 ◽

2009 ◽

Vol 114 (22) ◽

pp. 5030-5030

Author(s):

Silvia Rivas-Vera ◽

Mabel Oropeza-Borges ◽

Pedro Sobrevilla-Calvo

Keyword(s):

T Cell ◽

Health Center ◽

Hodgkin’S Lymphoma ◽

Prognostic Index ◽

Hodgkin's Lymphoma ◽

Anaplastic Lymphoma ◽

Non Hodgkin’S Lymphoma ◽

T Cell Lymphomas ◽

Non Hodgkin's Lymphoma ◽

Hodgkin's Lymphomas

Abstract Abstract 5030 Introduction T cell Non/Hodgkin's lymphomas (TCNHL) are a group of lymphomas characterized by an aggressive clinical course and resistance to the usual chemotherapy agents. Due to the limited availability of immunochemistry techniques the frequency and clinical presentation of these lymphomas are not well described in underdeveloped countries. Here we describe the experience with these diseases in a tertiary referral health center. Patients and methods We reviewed 520 cases with diagnosis of Non-Hodgkin's Lymphoma from the records of the Pathology Department of the Hospital General de Mexico, seen from January 2002 to July 2006. Results We found 80 cases with TCNHL (15.3%). In 62 cases the clinical information was available for review. We found a 1.45:1 male/female ratio, median age 32 years (range 17 to 83). Symptoms were present for a median of 6 months (range 1 to 120 months) before diagnosis. Regarding the pathological classification the Unspecified Peripheral T-cell lymphomas were more common (56%), followed by the anaplastic lymphoma (23%), T/NK (16%), Cutaneous lymphoma (3%) and angioimmunoblastic lymphoma (2%). In 56% the initial presentation was nodal and in 44% extranodal. The extranodal sites were: Nasal (34%), bone marrow (22%), pleura and lung (14%), parotid (5%), colon (5%), and liver (5%). Sixty seven percent of the patients had advanced clinical stages and 73% had at least 3 B symptoms. One quarter of patients had bulky disease at their first visit to our Hospital; the most frequent site was retroperitoneal (19%). The lactic dehydrogenase (LDH) was elevated in 89% of cases (range:97 U/L -3017 IU L, median 418 U/L); patients with anaplastic NHL had the highest values and NHL-TNK patients the lowest. HIV serology was performed in 41 of 62 patients. Ninety four percent of the patients had an ECOG between 1 and 3. We calculated the International Prognostic Index (IPI); it was low in 23 patients (37%), low-intermediate in 18 (29%), intermediate-high in 16 (26%) and high in just 5 patients (8%). When we classified the patients with the Prognostic Index for non-specific peripheral T-NHL (PIT or PTCL-L), we found that 79.4% of cases were in the high-risk group in contrast with 73.6% low group according to IPI. All patients were treated with CHOP chemotherapy. A complete response (CR) was achieved in 10 patients (16%); 13 patients (21%) were still on treatment at the end of the study, 4 patients (6.45%) did not respond to treatment and 14 patients (24.1%) had progressive disease. Ten patients discontinued treatment (16%) and 5 died (8.06%). At the end of the observation period 8 patients were alive without tumor activity, 2 patients were lost without tumor activity, 7 patients were alive with disease, 24 patients were missing with tumor activity, 9 patients were on treatment and 12 patients had died. Conclusions This study shows that in Mexico as in other populations, the TCNHL are less frequent than the B-cell lymphomas. It also confirms the poor response of the T-Cell lymphomas to CHOP. The population that attends our hospital is of a low socioeconomic stratum, and this fact explains the large abandonment of medical care. It is desirable the development of new drugs for these neoplasia. Disclosures No relevant conflicts of interest to declare.

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