Long term prognostic importance of primary Ki-1 (CD30) antigen expression and anaplastic morphology in adult patients with diffuse large-cell lymphoma

In order to assess long-term outcome of patients with localized (stage I or II) diffuse large-cell lymphoma treated with initial combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without involved-field radiotherapy following chemotherapy, we combined data from two prospective trials in Tucson (64 patients) and Vancouver (78 patients). Follow-up on 142 patients was updated and a variety of potential pretreatment prognostic factors were analyzed for impact on outcome. One hundred forty patients (99%) achieved a complete remission and there were no differences in outcome between institutions. Twenty-three patients have relapsed and 22 have died from lymphoma at a median follow-up of 4.4 years, resulting in an overall relapse-free survival of 82% at 5 years. There was no treatment-related mortality and were no instances of late cardiac toxicity or leukemia. Of the following potential pretreatment prognostic factors (age, stage, "B" symptoms, extranodal disease, gastrointestinal tract involvement, bulky disease, or disease above or below the diaphragm), only stage affected relapse-free survival (RFS) (P = .16) and survival (.003). Among 34% of patients over age 65, outcome was similar to younger patients. RFS for 108 patients treated with CHOP plus radiotherapy was not significantly superior to the use of CHOP alone in 34 patients (P = .2).

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Stage IV diffuse large-cell lymphoma: a long-term analysis.

Journal of Clinical Oncology ◽

10.1200/jco.1985.3.1.39 ◽

1985 ◽

Vol 3 (1) ◽

pp. 39-47 ◽

Cited By ~ 31

Author(s):

S Jagannath ◽

W S Velasquez ◽

S L Tucker ◽

J T Manning ◽

P McLaughlin ◽

...

Keyword(s):

Risk Factors ◽

Proportional Hazards Model ◽

Cell Lymphoma ◽

Stage Iv ◽

Large Cell ◽

Diffuse Large Cell Lymphoma ◽

Mediastinal Disease ◽

Large Cell Lymphoma ◽

Term Analysis

A long-term analysis of the clinical outcome of previously untreated adult patients who presented with stage IV diffuse large-cell lymphoma at diagnosis was performed to identify possible prognostic factors. Sixty-one patients were seen between 1974 and 1981; all were treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin followed by cyclophosphamide, vincristine, prednisone, and bleomycin for a total of one year. Overall five-year survival was 48.5%, with a median follow-up of 53 months. Of the 56 patients evaluable for remission status, 41 achieved a complete remission, and 27 are alive and disease free. Clinical factors of prognostic importance for survival included age, constitutional symptoms, lactate dehydrogenase (LDH) level, presence of mediastinal disease, large-cell infiltration of bone marrow, and number of extranodal sites of disease. The proportional hazards model then identified age, number of extranodal sites, and, to a lesser extent, serum LDH level as independent risk factors for survival. Four distinct patient risk groups were identified using these three factors. Younger patients with only one extranodal site of disease and normal LDH levels responded well on this therapy, with 100% alive at five years. In contrast, survival was less than 30% at five years for patients in the lowest risk group. There were 11 relapses; LDH level, constitutional symptoms, and mediastinal disease predicted for relapse. Knowledge of these risk factors permits individualization of treatment planning and allows more meaningful comparisons with the results of treatment studies using other intensive regimens.

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A 10-year update of CHOP-Bleo in the treatment of diffuse large-cell lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1986.4.10.1455 ◽

1986 ◽

Vol 4 (10) ◽

pp. 1455-1461 ◽

Cited By ~ 30

Author(s):

R Lee ◽

F Cabanillas ◽

G P Bodey ◽

E J Freireich

Keyword(s):

Cell Lymphoma ◽

Large Cell ◽

High Dose ◽

Diffuse Large Cell Lymphoma ◽

Actuarial Survival ◽

Conventional Dose ◽

Long Term Follow Up ◽

Large Cell Lymphoma

Long-term follow-up results of two studies using cyclophosphamide, doxorubicin, vincristine, and prednisone plus bleomycin (CHOP-Bleo) for the treatment of diffuse large-cell lymphoma are presented. Twenty-eight patients were treated with conventional-dose CHOP-Bleo and 36 patients with maximally tolerated doses of CHOP-Bleo. The maximal duration of follow-up was 10.5 years. The minimum follow-up was 5.7 years. Seventy-five percent of the conventional-dose group achieved a complete remission (CR) with a 10-year actuarial survival of 53% and a corresponding relapse-free survival (RFS) of 69% for CRs. Eighty-one percent of the high-dose group achieved CR, and the 10-year actuarial survival for all patients and RFS for CRs were 48% and 63%, respectively. The combined actuarial survival and RFS for both groups were 51% and 66%, respectively, at 10 years. For 11 patients with stage III disease, 91% achieved CR, 52% survived at 10 years, and the RFS was 67% for CRs. Seventy-five percent of 44 patients with stage IV disease achieved CR, 50% survived at 10 years, and the RFS was 67% for CRs. Three of the 16 relapses occurred late, between 30 to 65 months after initiation of therapy. Neuropathy occurred in 14 patients (22%). Five patients (8%) died of complications related to treatment. Five (8%) had clinically apparent, but nonfatal cardiopulmonary complications. The CHOP-Bleo regimen is an effective treatment for diffuse large-cell lymphoma, and is moderately well tolerated. The use of high-dose CHOP-Bleo for induction therapy did not result in any advantage after long-term follow-up.

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Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphoma

Nature ◽

10.1038/news010719-20 ◽

2001 ◽

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Large Cell ◽

Diffuse Large Cell Lymphoma ◽

Large Cell Lymphoma

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51 Small cell/lymphohistiocytic morphology is associated with CD8 positivity, retained T cell markers, a trend of decreased PD-L1 expression, but not outcome in adults with ALK+ ALCL

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0051 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A54-A54

Author(s):

Mahsa Khanlari ◽

Shaoying Li ◽

Roberto N Miranda ◽

Swaminathan Iyer ◽

Cameron Yin ◽

...

Keyword(s):

T Cell ◽

Anaplastic Large Cell Lymphoma ◽

Cell Lymphoma ◽

Large Cell ◽

Small Cell ◽

Adult Patients ◽

World Health ◽

Proliferation Index ◽

Cell Markers ◽

Large Cell Lymphoma

BackgroundSeveral morphologic patterns of ALK+ anaplastic large cell lymphoma (ALCL) are recognized: common, small cell, lymphohistiocytic, Hodgkin-like, and composite patterns.1 Small cell (SC) and lymphohistiocytic (LH) patterns are thought to be closely associated with poorer outcome in children with ALK+ ALCL.2 However, the clinicopathologic and prognostic features of SC/LH patterns of ALK+ ALCL are not yet reported in adults. Recently, we found PD-L1 expression in a large subset of ALK+ ALCL cases, however, PD-L1 expression in SC/LH versus non-SC/LH ALCL has not been reported.MethodsAmong 102 adult patients with ALK+ ALCL seen at our institution from January 1, 2007 through August 30, 2018, 18 (18%) cases had a SC and/or LH pattern. The clinical, pathologic, and outcome data were compared between SC/LH and non-SC/LH ALK+ ALCL cases using Fisher’s exact test. Overall survival (OS) was analyzed using the Kaplan-Meier method and compared using the log-rank test.ResultsThere were no significant differences in clinical features including age, gender, nodal versus extranodal involvement, B symptoms, stage, leukocytosis/lymphocytosis, and serum LDH levels between patients with SC/LH versus non-SC/LH ALK+ ALCL. Compared to non-SC/LH cases, SC/LH ALCL was more often positive for CD2 (92% vs. 36%, p = 0.0007), CD3 (81% vs. 15%, p = 0.0001), CD7 (80% vs. 37%, p = 0.03), and CD8 (54% vs. 7%, p = 0.0006). SC/LH ALCL showed a trend of decreased PD-L1 expression than non-SC/LH cases (24% vs. 46%, p = 0.11). There were no significant differences in the expression of CD4, CD5, CD25, CD43, CD45, CD56, TCR A/B, TCR G/D, cytotoxic markers, EMA, Ki-67 proliferation index. The induction chemotherapy and response rate in patients with SC/LH ALK+ ALCL were similar to patients with non-SC/LH ALK+ ALCL. After a median follow-up of 30.5 months (range, 0.3–224 months), there was no significant difference in OS between patients with SC/LH versus non-SC/LH ALK+ ALCL (p = 0.88).ConclusionsIn adults with ALK+ALCL, the SC/LH morphologic pattern is associated with a CD8+ T cell immunophenotype and retention of expression of T cell markers (CD2, CD3, and CD7). The trend of decreased PD-L1 expression in SC/LH ALCL suggests that these patients may not be ideal candidates for PD-L1 immunotherapy. The SC/LH patterns of ALK+ ALCL have no impact on the prognosis of adult patients which is in contrast to the reported association of the SC/LH patterns with poorer outcome in children with ALK+ ALCL.Ethics ApprovalThe study was approved by the Institutional Review Board at MD Anderson Cancer Center, Approval number: PA16-0897ReferencesSwerdlow SH, Campo E, The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375–2390.Brugières L, Deley MC, CD30 (+) anaplastic large-cell lymphoma in children: Analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology. Blood 1998;92:3591–3598.

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