CD30 Expression In Patients Research Articles

Issue Highlights-July 2021.

Issue Highlights-July 2021.

Flow cytometric assessment of CD30 expression in adult patients with acute leukemia

Background CD30, a member of tumor necrosis factor receptor superfamily, was originally identified as a cell-surface marker of Reed–Sternberg cell in classical Hodgkin lymphoma. CD30 is also expressed by several types of T-cell and B-cell non-Hodgkin’s lymphoma, such as anaplastic large cell lymphoma and primary mediastinal large B-cell lymphoma, and Epstein–Barr virus driven clonal lymphoproliferative disorder, as well as in reactive conditions such as infectious mononucleosis.Patients and methods A cross-sectional study was conducted at Clinical Hematology Department in Ain Shams University Hospital during a period from November 2016 to August 2017. A total of 20 new cases of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and 30 refractory/relapsed cases of AML and ALL either T or B, were enrolled in this study. CD30% expression was assessed by flow cytometry on bone marrow sample or peripheral blood.Results CD30 with cutoff more than 20% (+ve) was seen in 46% of cases, whereas cases with cutoff less than 20% (−ve) represented 54% of all leukemia cases. CD30 expression was higher in ALL, especially in T–acute lymphocyctic leukemia (T-ALL), with mean value of 44.564±27.158, with significant increase relapsed T-ALL (P=0.031) followed by B-ALL (23.988±15.678). CD30 expression in relapsed AML and ALL showed an increased percent but not yet statistically significant. Significant correlation was found in risk parameters as in white blood cells (WBCs) (>100 000) as well as Platlets (PLT) (<30 000) and CD30 expression in patients with T-ALL, with P values of 0.038 and 0.021, respectively, and nonsignificant difference between lactate dehydrogenase (LDH) and minimal residual disease in T-ALL and all risk parameters in B-ALL. Receiver operator characteristic (ROC) curve revealed that the accuracy of sensitivity and specificity was 69.9%.Conclusion CD30 has been shown to be a significant diagnostic tool in cases of acute leukemia especially in newly and relapsed T-ALL; moreover, it can be labeled to be a targeted therapy. Drug trials using monoclonal antibodies to CD30 as treatment in relapsed/refractory cases with special concern to response and survival rate are needed.

Utilization of a Novel Method of Detection of CD30 Expression in Diffuse Large B-Cell Lymphoma

Utilization of a Novel Method of Detection of CD30 Expression in Diffuse Large B-Cell Lymphoma

O1-16-3 - Prognostic significance of CD30 expression in patients with diffuse large B-cell lymphoma

O1-16-3 - Prognostic significance of CD30 expression in patients with diffuse large B-cell lymphoma

Analysis Of CD30 Expression in Patients With Diffuse Large B-Cell Lymphoma Treated at a Brazilian Universtiy Hospital

Analysis Of CD30 Expression in Patients With Diffuse Large B-Cell Lymphoma Treated at a Brazilian Universtiy Hospital

Outcomes by CD30 expression in patients with CTCL receiving brentuximab vedotin (BV) vs physician's choice (PC) in the Phase 3 ALCANZA study.

7517 Background: The Phase 3 ALCANZA study showed significant, durable responses with CD30-directed antibody-drug conjugate BV vs PC of methotrexate (MTX) or bexarotene (Bex) for CD30-positive (CD30+) cutaneous T cell lymphoma (CTCL). Uniform CD30 expression is characteristic of primary cutaneous anaplastic large cell lymphoma (pcALCL), but is variable among other subtypes including mycosis fungoides (MF). We examined activity of BV and MTX / Bex by CD30 expression in pts treated on the ALCANZA study. Methods: Adults with previously treated CD30+ MF or pcALCL were enrolled. MF pts had ≥2 skin biopsies from separate lesions, pcALCL had ≥1. Patients were scored CD30+ if ≥1 biopsy had ≥10% CD30+ lymphoid cells using an investigational Ventana diagnostic test, centrally assessed by one pathologist. We compared the proportion of MF subgroup pts (n=50 per treatment arm) with objective response lasting ≥4 months (ORR4; ALCANZA primary endpoint) and PFS in pts with all biopsies ≥10% CD30+ (CD30min ≥10%) vs ≥1 biopsy &lt;10% CD30+ (CD30min &lt;10%). Pts were randomized 1:1 to BV 1.8 mg/kg IV, Q3W, or PC for up to 16 three-week cycles. Results: 125/184 (68%) MF and 44/47 (94%) pcALCL pts were screened and scored CD30+. High inter-lesional variability in CD30 expression was seen in MF pts; 55/125 CD30+ MF pts (44%) had ≥1 biopsy with low (&lt;10%) or undetectable CD30. 100/125 CD30+ MF pts were eligible and enrolled. In the BV arm, ORR4 was higher in MF pts with CD30min ≥10% vs &lt;10%; median PFS with BV was higher in the CD30min &lt;10% group (Table). ORR4 with BV was greater than PC over all CD30 expression ranges (CD30min &lt;5%, 38% vs 13%; CD30 ≥5–≤20%, 35% vs 10%; CD30 &gt;20%, 76% vs 7%, respectively). Conclusions: Notable inter-patient or inter-lesional variability in CD30 expression was seen in MF pts. Highly superior ORR4 and PFS endpoints were seen with BV over PC regardless of CD30min expression level. Clinical trial information: NCT01578499. [Table: see text]

The expression of CD30 based on immunohistochemistry predicts inferior outcome in patients with diffuse large B-cell lymphoma.

The prognostic value of CD30 expression indiffuse large B-cell lymphoma (DLBCL)remains controversial. Herein, we performed this retrospective study to investigate the clinical and prognostic significance of CD30 expression in patients with DLBCL.Among all the 146 patients, the expression of CD30 was observed in 23 cases (15.7%).The DLBCL patients with CD30 expression showed more likely to present B symptoms, bone marrow involvement, non-germinal centre B-cell-like (Non-GCB) DLBCL, BCL-2 and Ki-67overexpression(p<0.05). Patients with CD30 expression showed significantly poor overall and event-free survivalcompared with CD30 negative patients(p = 0.031 and 0.041, respectively), especially those with the high intermediate/high-risk international prognostic index (IPI)(p = 0.001 and 0.007, respectively). The prognostic value of CD30expression retained in DLBCL patients treated with eitherCHOP (cyclophosphamide, doxorubicin, vincristine,prednisone) or R-CHOP(rituximab+CHOP). The multivariate analysisrevealed that the expression of CD30 remained an unfavorable factor for both overall and event-free survival (p = 0.001 and 0.002, respectively).In conclusion, these data suggest that CD30 is expressed predominantly in Non-GCBDLBCL. The expression of CD30 implied poor outcomein DLBCL patientstreated with either CHOP or R-CHOP, especially those with the high intermediate/high-risk IPI, possibly indicating that anti-CD30 monoclonal antibody could be of clinical interest.

Pathologic and Clinical Features Of CD30+ Post-Transplant Lymphoproliferative Disorders: A Large Retrospective Single Institutional Study

IntroductionB-cell post-transplant lymphoproliferative disorders (B-PTLD) represent a spectrum of lymphoid neoplasms arising as a consequence of impaired T-cell surveillance secondary to immunosuppressive medications. Epstein-Barr Virus (EBV) has been implicated in the development of B-PTLD. B-PTLDs diagnosed within one year post-transplant are more likely to be associated with EBV whereas B-PTLD diagnosed after a year are more likely to be EBV-negative and are associated with worse prognosis. Studies have shown that EBV up-regulates CD30 expression, a member of the TNF-receptor superfamily (Haque et al 2011). Novel agents are now available that target cells expressing CD30. Hence, knowledge of the expression profiles and the clinical characteristics of CD30+ neoplasms is warranted. In this study, we evaluated CD30 expression in 59 cases of B-PTLD and correlated CD30 and EBV status with clinical characteristics. MethodsConsecutive cases of B-PTLD diagnosed between 1997 and 2013 were retrieved from our archives. Immunohistochemistry (ISH) for CD30 was performed on formalin-fixed, paraffin embedded biopsies using the BerH2 monoclonal antibody (BioSB, Santa Barbara, CA) according to standard methods. Positive expression was pre-defined as CD30 expression by ≥20% of the lesional cells (Figure 1). Log-rank and Fischer's Exact 2-sided Test were performed in STATA 11, as appropriate. ResultsThe 59 B-PTLDs occurred in 54 patients. Three patients had two different sites biopsied during the diagnostic workup. Two other patients had recurrent B-PTLD. The median age at diagnosis was 22.8 years old (range 1.2 to 75.9 years); 65% were male. The median time from transplant to diagnosis was 2.6 years (range 6 weeks to 15.9 years, mean 4.2 years). Eighteen cases (35%) were diagnosed within the first year of transplantation. The organs transplanted are detailed in Table 1 with the percentage of CD30+ cases noted. Prior to transplantation, only 25/44 (57%) patients were EBV IgG seropositive, likely reflecting the number of children who were younger than age ten when transplanted (21/52; 40%). (Orjuela et al 2011). Serum EBV Polymerase Chain Reaction (PCR) was positive in 18/27 (67%) cases analyzed.Table 1Organ TransplantednPercentage CD30+Kidney1560%Heart2263%Lung3100%Heart-Lung1100%Liver1060%Pancreas10%Small Bowel1100%Bone Marrow1100%Pathological data are summarized in Table 2. In total, 39 of 59 cases (66%) showed 20% or more CD30 expression. Positive EBV ISH was significantly associated with CD30 expression (r=0.38, p< 0.01). Of 59 tumors informative for CD30 and EBV (by ISH), 32/41 of EBV-positive tumors were CD30 positive (78%) while 7 of 18 tumors that were EBV negative were CD30 positive (39%) (r=0.38 for the association of EBV and CD30 status, p=0.01). Detectable serum viremia was associated with CD30 status (r=0.49, p=0.02). There was no association found between CD20 status and CD30 status. There was no significant association between CD30 status and ki67 index or c-myc expression either (data not shown).Table 2HistologyCD 30 PositiveCD 20 PositiveEBER PositivePolymorphic (n=25)22/ 25 = 88%19/25= 76%22/25 = 88%Monomorphic: DLBCL (n=23)12/23 = 52%19/23 = 83%14/23 = 61%Monomorphic: Burkitt Lymphoma (n=3)1/3 = 33%3/3 = 100%1/3 = 33%Monomorphic:Plasmacytoma-like(n=8)4/8 = 50%4/8 = 50%4/8 = 50% ConclusionWe observed a high frequency of CD30 expression in patients with B-PTLD. Expression of CD30 correlates with ISH evidence of EBV infection in B-PTLD. In addition, positive serum EBV PCR was associated with CD30 expression. These two findings further support the link between EBV infection and CD30 expression. CD30 positivity was still found in 39% of EBER – negative cases, suggesting that CD30 ISH should be considered on all cases of B-PTLD. A monoclonal antibody conjugated to the cytotoxic agent MMAE,Brentuximab Vedotin (SGN-35), has shown activity in clinical trials against CD30 positive lymphomas (Jacobson et al 2012). Considering the relatively common prevalence of CD30+ expression in PTLD, brentuximab vedotin could be considered for study in combination with traditional front-line therapies or as an alternative therapy for relapsed/refractory disease. A prospective clinical trial (NCT 01805037) at Northwestern University is ongoing. Disclosures:Schecter:Seattle Genetics: Research Funding, Speakers Bureau. O'Connor:Seattle Genetics: Research Funding.

CD30 expression in acute lymphoblastic leukemia as assessed by flow cytometry analysis

We assessed CD30 expression in patients with acute lymphoblastic leukemia (ALL) of either T-cell or B-cell lineage to examine the potential benefit of anti-CD30-targeted therapy in this group of patients. Bone marrow specimens of 34 patients with T- and 44 with B-ALL were assessed for CD30 expression by multicolor flow cytometry immunophenotyping analysis. Of these 78 patients, 75 (96%) were adults; and 63 (81%) had refractory/relapsed disease. Using an arbitrary 20% cut-off, 13/34 (38%) cases of T-ALL and 6/44 (13%) cases of B-ALL were considered to express CD30. In five patients with T-ALL with sequential bone marrow tested, increased CD30 expression was observed during the course of high-dose chemotherapy (p = 0.025). Philadelphia chromosome/BCR–ABL1 fusion was positive in 14/44 cases of B-ALL and 2/32 cases of T-ALL, which showed no significant correlation with CD30 expression. In summary, we detected CD30 expression in approximately one-third of patients with T-ALL, and less frequently in B-ALL (p = 0.017). In T-ALL, CD30 expression is up-regulated during high-dose chemotherapy. These data indicate that anti-CD30-targeted therapy may be a potential option for patients with T-ALL with refractory/relapsed disease.

CD30 Expression in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndromes

We assessed for CD30 expression in patients with acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome (MDS) to examine the possibility that anti-CD30 could be targeted therapy in these patients. Multicolor flow cytometry immunophenotypic analysis was performed on bone marrow aspirates of 135 patients with AML or MDS and peripheral blood samples in a subset of 33 patients. Immunohistochemistry was performed on bone marrow aspirate clot specimens of 84 patients. The median patient age was 63 years (range, 13-92 years); 102 (75%) patients had refractory or recurrent disease, and 68 (50%) had high-risk cytogenetics. Overall, the median percentage of blasts positive for CD30 was 14% (range, 0%-91%). By using an arbitrary 20% cutoff, 49 (36%) patients were considered to have CD30 expression. Monocytic cells, either mature or immature, were consistently negative for CD30. Therefore, CD30 expression was less in AML with monocytic differentiation (P = .006). The patients with persistent disease who had been actively treated had a higher level of CD30 expression than the patients who were untreated (P = .031). In paired samples, CD30 expression was consistently higher in bone marrow blasts than in peripheral blood blasts (P = .002). Immunohistochemistry demonstrated CD30 expression by myeloblasts in a subset of patients, but reactivity was generally weaker and focally compared. CD30 is expressed by myeloblasts in a substantial subset of patients with AML or MDS. Because the study group was composed mostly of patients with high-risk AML or MDS in whom very few treatment options are available, these data raise the possibility that anti-CD30-targeted therapy could be a potential option for this patient group.

A Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory CD30-Positive Non-Hodgkin Lymphomas: Interim Results.

A Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory CD30-Positive Non-Hodgkin Lymphomas: Interim Results.

Altered Expression of the Lymphocyte Activation Markers CD30 and CD27 in Patients with Pouchitis

Background: The mechanism underlying the development of ileal pouch inflammation in ulcerative colitis patients (pouchitis) after restorative proctocolectomy is unclear. Persistent systemic T cell activation or expansion of specific memory cell populations could predispose certain patients to develop local inflammation within the neo-rectum. Therefore, the aim was to study the expression of the lymphocyte activation markers CD27, CD30, CD25 and CD69 on the CD45RO+ memory cell subset of isolated peripheral blood mononuclear cells (PBMC), soluble CD30 levels and mucosal CD30 expression in patients with pouchitis and in controls. Methods: Flow cytometry was performed on PBMC isolated from patients with pouchitis (n = 9), without pouchitis (n = 10) and normal controls (n = 9). Serum CD30 was measured in patients with pouchitis (n = 25), without pouchitis (n = 26) and normal controls (n = 20) by ELISA. CD30 expression was quantified in pouchitis (n = 15) and normal pouch (n = 15) mucosa using a three-stage immunoperoxidase method. Results: Naïve CD45RO-CD27+ PBMC were significantly decreased in pouchitis (25.6%) compared to normal controls (34.4%), (P = 0.03). CD30, CD25 and CD69 subsets did not differ between the groups. Serum CD30 was increased in pouchitis patients 58 (1-380) U/ml compared to non-pouchitis 16.5 (1-290) U/ml, P = 0.007, and normal controls 11 (2-80) U/ml, P = 0.0005. In the mucosa, the numbers of CD30+ cells were increased in pouchitis compared to noninflamed pouches (P = 0.02). Conclusions: Increased sCD30 in pouchitis is associated with elevated mucosal expression. Of the activation markers studied, only the circulating naïve CD27+ population differed in pouchitis patients compared with controls. The observed decrease in this cell type may reflect antigen priming and subsequent loss of CD27 implying that antigen driven activation of specific T cell subsets may occur in pouchitis.

CD30 induction and cytokine profiles in hepatitis C virus core-specific peripheral blood T lymphocytes.

Since an efficient control of virus infections may depend on the appropriate lymphokine profile, we studied cytokine responses and CD30 induction, a recently proposed surrogate marker of type 2 cells, in 10 healthy anti-hepatitis C virus (HCV)-seropositive blood donors without viremia (group A) and in 15 patients with hepatitis C (group B). Intracytoplasmic IFN-gamma, IL-2, IL-4, and IL-10 were determined by triple-color flow cytometry in the CD3+ and CD3+/CD30+ lymphocyte subsets after stimulation of PBMC with rHCV core protein and five core-derived peptides corresponding to the four immunodominant Th epitopes C.T1 to C.T4. In group A, more type 1 cytokines were induced by the rHCV core protein and all immunodominant core peptides (p < 0.05), whereas IL-10-producing T cells were found more frequently in group B. Induction of CD30+ T cells was found almost exclusively in group B (p < 0.01). The difference in cytokine responses was due to the CD3+/CD30- T cell subset and not the CD3+/CD30+ subset, which predominantly produced both IL-10 and IFN-gamma, but only small amounts of IL-2 and IL-4. We conclude that immunodominant HCV core peptides induce preferentially type 1 cytokines in healthy anti-HCV-positive blood donors and CD30 expression in patients with chronic hepatitis C. However, in both groups, CD30+ T lymphocytes produce an intermediate Th0-like cytokine profile. Thus, chronicity in HCV infection may reflect a lack of type 1 cytokine production.