ALK-negative Anaplastic Large Cell Research Articles

PRELIMINARY RESULTS OF A PHASE 2 STUDY OF CHIDAMIDE, GEMCITABINE, VINORELBINE, AND MITOXANTRONE LIPOSOME (CHI‐GVM) IN RELAPSED/REFRATORY PERIPHERAL T‐CELL LYMPHOMA

Introduction: Patients with relapsed or refractory peripheral T-cell lymphoma (R/R PTCL) have a poor prognosis. There is no effective treatment for these patients. Mitoxantrone hydrochloride liposome showed high antitumor activity and low toxicity in lymphoma. In a phase II clinical study of mitoxantrone hydrochloride liposome monotherapy for R/R T-cell lymphoma, the overall response rate (ORR) and complete remission rate (CRR) of PTCL, not otherwise specified (PTCL, NOS) reached 34.4% and 18.8%. Our study aimed to explore whether the combination chemotherapy regimen containing mitoxantrone liposomes can improve the efficacy and survival of R/R PTCL. Methods: A Phase II, multicenter, single-arm, open-label study is planned at our center. All patients enrolled are R/R PTCL and will receive induction therapy with chidamide (20 mg, twice a week), gemcitabine (1 g/m2, d1), vinorelbine (20 mg/m2, d1), and mitoxantrone hydrochloride liposome (20 mg/m2, d1) (Chi-GVM) for 2–4 cycles. Patients aged 60 years or younger with complete remission (CR) / unconfirmed complete remission (CRu) / partial remission (PR) after 2–4 cycles of induction therapy received autologous stem cell transplantation (ASCT) prior to maintenance therapy. Patients after ASCT or patients over 60 years old with CR/CRu/PR receive maintenance therapy of chidamide (20 mg twice a week) until intolerance or disease progression (PD). Efficacy was assessed by contrast-enhanced CT or PET-CT every 2 cycles during treatment. The primary endpoint of the study was ORR and secondary endpoint was duration of remission (DOR) and1-year progression-free survival (1y-PFS). Results: A total of 7 patients were treated with Chi-GVM between September 2022 and February 2023, including 3 patients with PTCL, NOS; two patients with ALK negative anaplastic large cell lymphoma (ALCL, ALK-); and 2 patients with monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). Five male and two female were included, with a mean age of 57 years, and one patient was post-ASCT. Two patients were re-staged of stage I–II and five of stage III–IV prior to treatment, extranodal lesions including stomach, skin and intestinal. Four patients were evaluable for efficacy, 1 patient was lost to follow-up, and 2 patients did not reach the assessment time. Of the evaluable patients, 2 patients had a best response of CR and 2 patients experienced PD, one patient achieved CR and received consolidation therapy with ASCT. Grade 2 or 3 adverse events occurred in 5 patients, including 3 cases of leukopenia, 4 cases of neutropenia, 2 case of thrombocytopenia, and 1 case of hepatic insufficiency. One patient had myocardial damage before treatment, and kept stable after mitoxantrone hydrochloride liposome used. Keywords: Aggressive T-cell non-Hodgkin lymphoma, Chemotherapy, Late Effects in Lymphoma Survivors No conflicts of interests pertinent to the abstract.

PRDM1 Deletion and STAT3 Mutations Cooperatively Promote CD8+ T-Cell and NK-Cell Growth in Vitro

PRDM1 loss and STAT3 activating mutations commonly co-occur in several non-Hodgkin lymphomas, including ALK negative Anaplastic Large Cell Lymphoma (ALCL) and NK-cell lymphoma (NKCL). PRDM1 is a tumor suppressor gene in NKCL, and also plays important roles in the homeostasis and differentiation of CD8+ T-cells. STAT3 encodes a critical transcription factor involved in specific cytokine-mediated JAK/STAT pathway activation in lymphocytes, controlling proliferation, apoptosis, and other cellular functions. However, it remains unclear whether these two abnormalities cooperate during lymphomagenesis. Here, we introduced PRDM1 deletion and STAT3 mutants into primary human T- or NK-cells isolated from PBMCs of healthy donors and performed functional studies on the genetically modified cells. When either of the two common STAT3 mutants, STAT3Y640F or STAT3D661Y, was transduced into T- or NK-cells, the transduced cells showed short term growth advantage but could not persist, indicating that STAT3 activating mutations may provide stimulatory signals to T- and NK-cells initially, but inhibitory pathways could be activated that prevent long-term sustainable growth. When we knocked out PRDM1 first and then transduced the cells with the STAT3 mutants, the double modified T- or NK-cells showed sustained competitive growth advantage during in vitro culture. The effects were specific to STAT3 mutants as transduction of wild-type (WT) STAT3 or the STAT5BN642H mutant did not improve cell growth. These findings suggest that PRDM1 loss and STAT3 mutations synergistically promote growth in primary T- and NK-cells. We further showed that PRDM1-null, STAT3Y640F-transduced NK-cells displayed better survival and growth compared to PRDM1-deleted or WT cells with feeder cell stimulation. More importantly, the double mutant NK-cells were more independent of feeder cell stimulation, and they were able to expand when supplemented with a single cytokine (IL-15 or IL-2). This feature may be relevant to lymphoma development in vivo where stimulatory cytokines may be limiting. In addition, these double mutant NK-cells had reduced expression of exhaustion markers Tim-3 and Tigit. Similarly, genetically modified CD8+ T cells with PRDM1 knockout and STAT3-mutant were found to express much lower levels of PD-1, Tim-3, and Tigit, an important feature that may promote their growth in vivo where ligands of these co-inhibitory molecules may be expressed in the microenvironment. These double mutant CD8+ T cells exhibited greater stem memory (Tscm) phenotype, marked by CD45RA+, CD62L+, and CCR7+, suggesting the switch to a memory rather than an effector program. Taken together, our in vitro experiments using primary human cells have provided evidences for the functional cooperation between PRDM1 loss and STAT3 activating mutation in promoting CD8+ T- and NK-cell growth. Some features shown by the double mutant cells may facilitate their survival and growth more significantly in vivo. We are currently investigating the adoptive transfer of modified mouse or human cells into littermates or NSG-Tg(huIL15) mice respectively to observe the in vivo development and evolution of the transferred cells. The detailed mechanistic interactions between these two genetic abnormalities in lymphoma development will be further investigated.

The Addition of Romidepsin to CHOEP and High-Dose Chemotherapy Plus Stem Cell Transplantation Did Not Ameliorate the Outcome of Untreated Angioimmunoblastic T-Cell or Follicular T-Helper Lymphoma: Subgroup Analysis of Phase II FIL-PTCL13 Study

Introduction: In the phase Ib/II study PTCL13 study (NCT02223208) we demonstrated feasibility of Romidepsin 14 mg/mq in addition to CHOEP followed by high-dose chemotherapy and stem cell transplantation (SCT), but no benefit was observed in term of progression free survival (PFS), and the enrollment of the trial was stopped due to inefficacy of the experimental combination. Other studies showed Romidepsin activity in relapsed or refractory PTCLs, especially in angioimmunoblastic (AITL) subtype, expecially when combined with azacytidine. On this basis, we conducted a sub-analysis of the PTCL13 trial, with the aim to evaluate the role of adding Romidepsin to CHOEP followed by high dose chemotherapy and SCT in newly diagnosis AITL and T-helper follicular lymphoma patients. Methods: Patients aged 18-65 eligible to SCT, with advanced PTCL-NOS, AITL/T-helper follicular and ALK negative anaplastic large cell lymphoma, were eligible to PTCL13 study. Treatment plan consisted of 6 courses of Ro-CHOEP every 21 days (14 mg/ms Ro day 1 and 8), followed by cisplatin-cytarabine-dexamethasone (DHAP) with stem cell harvest and SCT. Patients in complete response (CR) after induction proceeded to autoSCT, while those in partial response (PR), with an available HLA-matched donor, proceeded to alloSCT upfront. Results: 89 patients were enrolled into the phase Ib and II part of the study; median age was 55 years (IQR 49;60); 78 (91%) had stage III-IV and 31 (36%) IPI risk >2. Pathological materials were collected at the time of diagnosis, and centrally reviewed by expert hemo-pathologist; subgroups were: 34 PTCL-NOS, 21 ALK negative and 31 AITL/THF. The clinical characteristics of the 31 AITL/THF patients were: median age 56 years (IQR 52.5-59.5), 63% male, 31% had an intermediate-high IPI score risk and 50% had a bone marrow involvement at diagnosis. The overall response (ORR) at the end of induction with 6 Romidepsin-CHOEP was achieved in 7 AITL/THF patients (22%), with 6 (19%) patients in complete remission (CR); at the end of treatment, the ORR was observed in 15 (47%) AITL/THF patients. ORR and CR results are superimposable to those of the whole population. At a median follow-up of 28 months, the 24-months PFS for AITL/THF was 43% (95% CI: 0.22-0.61) compared to 24-months PFS for ALK-negative 37% (95% CI: 0.16-0.59) and for PTCL-nos 33% (95% CI: 0.18-0.48), p 0.136; the 24-months OS for AITL/THF was 78% (95% CI: 0.57-0.89) compared to 24-months OS for ALK-negative 63% (95% CI: 0.37-0.81) and for PTCL-nos 61% (95% CI: 0.40-0.76), p 0.556. Conclusions: In the FIL-PTCL13 the primary endpoint was not met and the enrollment of the trial was stopped due to inefficacy of the experimental combination. With the limits of the small number and the unpowered analysis, the benefit of adding romidepsin to chemotherapy was not observed in the subgroup AITL/THF patients, even if the PFS and the OS of this subgroup seem better than the others.

A Pilot Study Using Nivolumab in Combination with Standard of Care Chemotherapy in Newly Diagnosed Peripheral T-Cell Lymphomas

A Pilot Study Using Nivolumab in Combination with Standard of Care Chemotherapy in Newly Diagnosed Peripheral T-Cell Lymphomas

Adding Romidepsin to CHOEP in First Line Treatment of Peripheral T-Cell Lymphomas Does Not Improve the Response Rate: Final Analysis of Phase II PTCL13 Study

Adding Romidepsin to CHOEP in First Line Treatment of Peripheral T-Cell Lymphomas Does Not Improve the Response Rate: Final Analysis of Phase II PTCL13 Study

Abstract 3005: Establishment and characterization of a series of lymphoma PDX models representing varied clinical behaviors and treatment responses

Abstract Background: Lymphomas are comprised of a heterogeneous group of hematologic malignancies based on different origins with diverse patterns of clinical behavior and treatment response. Pathologically, lymphomas are divided into two main subtypes, Hodgkin (HL) and non-Hodgkin (NHL), which account for around 10% and 90% of cases, respectively. NHL is further divided into B cell, T cell and natural killer (NK) cell subtypes. Besides histopathology, cancer is increasingly recognized as a genetic disease with specific molecular alterations, such as ALK translocation in anaplastic large cell lymphoma, MYC/BCL2/BCL6 translocation in B cell lymphoma (often referred to as ‘double-hit' or ‘triple-hit') and other specific mutations or overexpression. Current clinical therapeutic options for lymphoma therefore need to consider not only the histological type, clinical aggressiveness and cancer stage, but also the molecular markers, cytokine signaling, epigenetic aberrations and lymphoma microenvironment. Preclinical modeling with diverse types of lymphomas and deep characterization are important for the drug discovery of new lymphoma treatments. Methods: We have established and characterized a number of different subtypes of lymphoma patient-derived xenograft (PDX) models including both mature T/NK cell neoplasms and B cell neoplasms. Immunodeficient mice were used for establishment of these lymphoma PDX models with subcutaneous or tail vein engraftment. Model classification and characterization were determined by histopathology and IHC, as well as genomic profiling by next-generation sequencing (NGS) and response to chemo- or targeted therapies. Results: We have developed and characterized a large panel of lymphoma PDX models with various subtypes, including mantle cell lymphoma, angioimmunoblastic T cell lymphoma, ALK negative anaplastic large cell lymphoma, adult T cell leukemia/lymphoma, peripheral T cell lymphoma, extranodal NK/T cell lymphoma and also other common B cell lymphomas such as DLBCL and follicular lymphoma. Histopathology analysis of these models is in line with clinical pathology diagnosis. Additionally, cancer type-specific biomarkers, such as CD3, CD20, BCL2, BCL6 and MYC, were used for characterization of these lymphoma models by IHC. The response to subtype-specific chemotherapy or targeted therapies, such as CHOP, BTK inhibitors, CD38 antibodies etc., are now tested in some of these lymphoma PDX models and will be presented at the meeting. Conclusions: Lymphomas have diverse subtypes, represented by different clinical features and treatment responses. We have established and characterized a series of lymphomas with varied types including a large cohort of B cell lymphoma and T/NK cell lymphoma PDX models for drug evaluation. Citation Format: Jessie J. Wang, Yanrui Song, Jitai Zheng, Guiqing Wu, Likun Zhang, Henry Q.X. Li, Davy Xuesong Ouyang. Establishment and characterization of a series of lymphoma PDX models representing varied clinical behaviors and treatment responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3005.

Peripheral Blood Involvement By Flow Cytometry As a Prognostic Factor in Aggressive T Cell Lymphomas Following Autologous Stem Cell Transplantation

Introduction: Aggressive T cell lymphomas (TCL) are a heterogenous group of lymphomas that are frequently associated with poor outcomes. Autologous stem cell transplantation (ASCT) is recommended according to the NCCN guidelines and by practice standards for most subtypes as a consolidation for patients in first remission. A large prospective study of up-front ASCT by the Nordic Lymphoma group identified age, ECOG performance status <2, and bone marrow involvement as important prognostic factors. We have identified peripheral blood involvement by flow cytometry at diagnosis in up to one third of patients with aggressive TCL and analyzed whether this was a prognostic factor for outcomes after ASCT. Methods: We retrospectively analyzed data from consecutively treated patients (pts) with aggressive T-cell lymphomas who underwent ASCT at our institution from July 2009 to February 2019. Patient and disease characteristics were summarized using descriptive statistics. Kaplan-Meier analysis was used to estimate progression free survival (PFS) that was defined as the time from SCT to the first evidence of recurrence, and overall survival (OS) that was defined as the time from SCT to death or last institutional follow up with a hematologist. We collected data on age, co-morbidities, disease subtype, stage, response to therapy and treatment both pre and post SCT. Flow cytometry was obtained at diagnosis and phenotype of atypical circulating cells was compared with immunophenotype from tumor biopsy specimens. Results: 50 pts with TCL who received ASCT were identified for this analysis. Of this population, 41 (80%) of pts had peripheral blood flow available at the time of initial diagnosis. T-cell lymphoma types included peripheral T cell lymphoma not otherwise specified (PTCL NOS, 17 pts), angioimmunoblastic T cell lymphoma (AITCL, 15pts), ALK negative anaplastic large cell lymphoma (ALCL, 1pt), enteropathy-type T-cell lymphoma (EATL, 2pts), extranodal natural killer T-cell lymphoma (NKTCL, 2pts) and panniculitis like T cell lymphoma (2 pts) (Table 1). Median age of the cohort was 62 years (range 20-75 years) and all patients included had an ECOG PS 0-1 at the time of diagnosis. The majority had stage 4 disease (36/41, 87.8%), but analysis included a small number of patients with stage 2 (1/41, 2.4%) and stage 3 (4/41,9.7%) disease. Bone marrow involvement by morphologic criteria was noted on bone marrow biopsy in 8/41 (19.5%) pts; bone marrow was negative in 28/41 or 61% pts and not evaluated in 8/41 or 19.5% pts. Flow cytometry of peripheral blood performed as part of initial staging was positive for circulating malignant cells in 13/41 pts (31.7%) at the time of diagnosis. All patients underwent ASCT in first remission. The median PFS and OS were 15.2 and 29.9 months respectively in the flow positive group, while neither median PFS nor OS were reached in the flow negative group (Figures 1 and 2). Flow cytometry results from time of diagnosis was not strongly associated with PFS (log rank, p = 0.39), however, it was associated with overall survival (log rank, p = 0.012). There were 11 deaths in the cohort- 4 in the flow negative group and 7 in the flow positive group. Further, when bone marrow involvement was evaluated, 7 of 13 pts with positive flow cytometry (53.8%) and 5 of 28 (17.8%) pts with negative flow cytometry had BM involvement, suggesting a correlation between positive bone marrow and detection of lymphoma cells in the peripheral blood at the time of diagnosis. Conclusions: We demonstrate in our cohort of patients that detection of circulating lymphoma cells at diagnosis by flow cytometry was associated with a worse outcome in patients with aggressive T cell lymphomas undergoing ASCT as a consolidation in first remission. Larger cohorts will be needed to validate these findings, but these results suggest peripheral blood involvement by sensitive flow cytometry may identify patients with worse outcomes who might benefit from a more aggressive strategy such as allogeneic stem cell transplantation or alternative consolidation strategies. Disclosures Huntington: Bayer: Consultancy, Honoraria; Pharmacyclics: Honoraria; Celgene: Consultancy, Research Funding; DTRM Biopharm: Research Funding; Genentech: Consultancy; AbbVie: Consultancy. Isufi:Celgene: Consultancy; Novartis: Consultancy; Astra Zeneca: Consultancy. Foss:Seattle Genetics: Consultancy, Other: fees for non-CME/CE services ; Mallinckrodt: Consultancy; miRagen: Consultancy; Spectrum: Other: fees for non-CME/CE services ; Eisai: Consultancy; Acrotech: Consultancy.

A Phase II Study of Nivolumab in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma

A Phase II Study of Nivolumab in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma

Detection of chromosomal translocations of DUSP22 and TP63 in ALK-negative anaplastic large cell lymphoma by fluorescence in situ hybridization and related clinical relevance

Objective: To correlate chromosomal translocations of DUSP22 or TP63 with clinical significance in ALK-negative anaplastic large cell lymphoma (ALK(-)ALCL). Methods: Thirty-two patients with ALK(-)ALCL were selected from January 2004 to January 2014 at Fujian Provincial Hospital for the detection of chromosomal translocations of DUSP22 and TP63 by fluorescence in situ hybridization (FISH). The relationship between DUSP22 and TP63 chromosomal translocations and the clinicopathological parameters of ALK(-)ALCL was analyzed. Results: Among the 32 ALK(-)ALCL patients, 7(21.8%) had DUSP22 gene rearrangement (DUSP22(+)ALK(-)ALCL). Three patients (9.4%) had TP63 gene rearrangement (TP63(+) ALK(-)ALCL). There were 22 patients (68.8%) without rearrangement of either DUSP22 or TP63 (DUSP22(-)TP63(-)ALK(-)ALCL). The patients with DUSP22(+) ALK(-)ALCL were among the younger, and the patients with TP63(+) ALK(-)ALCL were among the elder. The mean age of patients with DUSP22(-)TP63(-)ALK(-) ALCL was between those of DUSP22(+)ALK(-)ALCL and TP63(+) ALK(-)ALCL (P<0.05). Based on Ann Arbor staging, incidence of DUSP22 gene rearrangement decreased as the clinical stage of ALK(-)ALCL increased (P<0.05). Incidence of TP63 gene rearrangement cases increases in patients at more advanced clinical stage(P<0.05). The five-year survival rate and prognosis of patients with DUSP22(+)ALK(-)ALCL were the highest. Patients with TP63(+) ALK(-)ALCL had the lower five-year survival and the worse prognosis (P<0.05). Conclusion: Presences of DUSP22 and TP63 chromosomal translocations correlate with the clinical stages and prognosis of ALK(-)ALCL and may be used for the differential diagnosis, determination of tumor aggressiveness and prognostication of ALK(-)ALCL.

Clinicopathological characteristics of adult T cell leukemia/lymphoma

Objective: To investigate the clinical presentation, clinicopathologic features, diagnosis and differential diagnosis of adult T cell leukemia/lymphoma (ATLL). Methods: Four cases of ATLL from Fujian Cancer Hospital between October 2017 and May 2018 were analyzed using hematoxylin-eosin and immunohistochemical stains and polymerase chain reaction (PCR) for HTLV-1 provirus genes. The relevant literature was reviewed. Results: There were two males and two females, age range 38-80 years. All patients were from coastal cities of Fujian province. Clinical presentations including lymphadenopathy, hepatomegaly and splenomegaly were detected in most patients; skin lesion, hypercalcemia and lymphocytosis were also commonly detected.Histologically, there was diffuse effacement of the normal architecture by tumor cells infiltration. The inflammatory background is usually sparse, with scanty eosinophils. The atypical lymphoid cells were typically medium to large sized with pronounced nuclear pleomorphism, irregular nuclei, chromatin clumping and prominent nucleoli. Blast-like cells with transformed nuclei were present in variable proportions. Giant cells with convoluted or cerebriform nuclear contours may be present. Rare cases may be composed predominantly of anaplastic tumor cells. Characteristic "flower cells" with large multi-lobated nuclei can be seen. The tumor cells were strongly positive for CD2, CD3, CD5, CD4 and CD25, but negative for CD7, CD8 and cytotoxic molecules (including TIA-1, Granzyme B and perforin). In three cases, the large transformed cells were positive for CD30. In one case, the anaplastic large cells were diffusely and strongly positive for CD30. All cases were negative for EBER, but positive for HTLV-1 provirus. Conclusions: ATLL is a rare type of T cell lymphoma with unique clinical and pathological features, and should be distinguished from peripheral T cell lymphoma, NOS, ALK negative anaplastic large cell lymphoma and mycosis fungoides. Hypercalcemia, systemic disease, characteristic "flower cells" and specific immunophenotypic profile of CD3(+), CD4(+), CD25(+), and CD7(-) are highly suggestive. However, ATLL can only be confirmed if the presence of HTLV-1 provirus.

An unusual case of sarcomatoid alk negative anaplastic large cell lymphoma

Anaplastic large cell lymphoma (ALCL) has a number of morphological variants that can pose diagnostic challenges. One of the rarest variants is the sarcomatoid variant, with the literature on this neoplasm limited to sporadic case reports. Sarcomatoid ALCL consists of large, often spindled neoplastic cells that can mimic a soft tissue sarcoma, anaplastic carcinoma or melanoma. This confusion may be confounded by the fact that many cases are anaplastic lymphoma kinase (ALK) negative. We report the case of a 66-year-old male presenting with multiple right axillary masses. A core biopsy of one of these revealed the normal nodal architecture to be effaced by a population of large, anaplastic epithelioid and spindled cells arranged in a vaguely fascicular and storiform architecture. Immunohistochemistry revealed the lesion to be strongly positive for CD30, as well as CD45. Positive staining was also seen with the T cell markers CD4 and CD7, as well as a number of cytotoxic markers. Following an expert opinion being sought, a diagnosis of ALK negative anaplastic large cell lymphoma with sarcomatoid morphology was rendered.

A Comparison Study Between Allogeneic and Autologous Hematopoietic Stem Cell Transplant for High-Risk Peripheral T-Cell Lymphomas (PTCL)

Objective: To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma (PTCL).Methods: From July 2007 to July 2014, 60 cases of high risk PTCL were analyzed retrospectively.Results: All 60 patients were at high risk group (carried with IPI≥3), with a median age of 31 (13-55) years old. Of the 60 cases, 22 were PTCL-not otherwise specified (PTCL-NOS), 22 with ALK negative anaplastic large cell lymphoma (ALK-negative ALCL) and 16 with angioimmunoblastic T-cell lymphoma (AITL). Twenty-one (21/60) received allo-HSCT and thirty-nine patients (39/60) received auto-HSCT. Before receiving transplantation, 40/60 patients were in complete remission (CR), 2/60 patients were partial remission (PR) and 18/60 patients were not remission (NR). In the 40 CR patients before transplant, 10 patients received allo-HSCT and 30 patients received auto-HSCT. In the 20 PR/NR patients before transplant, 11 patients received allo-HSCT and 9 patients received auto-HSCT. After a median follow-up of 39 (range 1-96) months, the K-M analysis showed that the 5-year PFS for auto-HSCT and allo-HSCT were 61% and 60% (P = 0.724). The 5-year OS for auto-HSCT and allo-HSCT were 62% and 61% (P = 0.724). There were no statistically significant differences between the auto-HSCT and allo-HSCT. And the cumulative TRM of allo-HSCT and auto-HSCT were 16.5% and 0 (P=0.250) within 5-years after transplantation. At the end of the last follow-up, 7 patients relapsed in auto-HSCT group and 2 patients relapsed in allo-HSCT group, the 5-year cumulative recurrence rates of auto-HSCT and allo-HSCT transplantation were 37.2% and 10.1% (P=0.298), respectively.Conclusion: There was no significant difference in the long-term survival between auto-HSCT and allo-HSCT for high risk PTCL patients. The effect of allo-HSCT may be better for NR patients. DisclosuresNo relevant conflicts of interest to declare.

Comparison of allogeneic or autologous hematopoietic stem cell transplant for high-risk peripheral T cell lymphomas

目的比较自体造血干细胞移植（auto-HSCT）和异基因造血干细胞移植（allo-HSCT）治疗高危外周T细胞淋巴瘤（PTCL）疗效的差异。方法回顾性分析苏州大学附属第一医院60例接受HSCT治疗的高危PTCL患者临床资料。结果60例PTCL患者均为高危组患者（IPI评分≥3分），接受移植时中位年龄31 (12~58）岁。包括PTCL非特指型22例、ALK阴性的间变大细胞淋巴瘤22例、血管免疫母细胞淋巴瘤16例。其中接受auto-HSCT的有39例（63.5%），接受allo-HSCT的有21例（36.5%）。移植前40例完全缓解（CR），2例部分缓解（PR），18例未缓解（NR）。40例CR患者中10例接受allo-HSCT, 30例接受auto-HSCT。20例PR+NR患者中11例接受allo-HSCT, 9例接受auto-HSCT。移植后中位随访时间为39 (1~96）个月，auto-HSCT和allo-HSCT组的5年无进展生存率分别为61％和60%（P=0.724）。auto-HSCT和allo-HSCT组的5年总生存率分别为62％和61%（P=0.724）。auto-HSCT和allo-HSCT组的5年移植相关死亡率分别为22.7％和41.8%（P=0.250）。截至末次随访时间，auto-HSCT中7例患者复发，allo-HSCT组中2例复发，auto-HSCT和allo-HSCT组的5年累计复发率分别为37.2％和10.1%（P=0.298）。结论高危PTCL患者选择auto-HSCT或allo-HSCT治疗长期生存无明显差异，但allo-HSCT组患者移植前多为NR状态，表明对于NR患者，allo-HSCT效果可能较好。

Tissue Is the Issue: Accuracy of PET Imaging to Detect Bone Marrow Clearance in Patients with Peripheral T-Cell Lymphoma

INTRODUCTION:Adult mature T- and NK-cell neoplasms are a heterogeneous group of aggressive lymphomas comprising approximately 10% to 20% of all non-Hodgkin lymphomas (NHL) with an estimated 5-year overall survival of 40%. Staging and treatment strategies are guided by malignant involvement on PET/CT scan and bone marrow (BM) biopsy. The Lugano Criteria, established in 2014, suggested that focal FDG uptake within the bone marrow was highly sensitive for both Hodgkin (HL) and diffuse large B-cell lymphoma (DLBCL) potentially obviating the need for a bone marrow biopsy if no lesions were seen. Limited data exist regarding the sensitivity of PET for BM involvement in T-cell lymphoma. This study compares PET/CT scans and repeat BM biopsy in patients who have undergone treatment for peripheral T-cell lymphomas (PTCL) by evaluating BM avidity on PET scans.METHODS:This is a single institution study using the Mayo Clinic Lymphoma Database between January 1, 2001 and January 1, 2015. We retrospectively identified all patients with a diagnosis of PTCL, biopsy proven BM involvement at diagnosis, and a concomitant PET for staging. Patients were then reviewed to assess completion of induction therapy and availability of both PET/CT and bone marrow results post-therapy. Evaluation for concordance and discordant BM involvement were then determined using BM biopsy as the gold standard.RESULTS:Sixteen patients had both PET/CT and BM biopsy after completing induction therapy. Median age at diagnosis was 63 years (range 34-72) and 69% were male. PTCL subtype was peripheral T-cell lymphoma, not otherwise specified in seven patients; ALK negative anaplastic large cell lymphoma in one patient; and angioimmunoblastic in 8 patients. Pre-treatment PET/CT scans demonstrated eight patients (50%) with false negative scans. Post-treatment biopsy results demonstrated that ten (62.5%) had biopsy proven residual bone marrow involvement after induction. Eight patients (50%) were found to have BM biopsy proven disease with a negative PET scan. Two patients (12.5%) had both positive BM biopsy and PET scans; 5 patients (31.3%) had negative BM biopsies and PET scans. One patient (6.25%) had a negative BM biopsy, but had a PET scan that revealed positive disease. This patient was considered to have had a false positive PET scan and indeed has remained in remission since April 2009 without any further relapse or treatment. Sensitivity of PET for BM involvement was very poor at 20% (2/10) with a specificity of 50% (2/4) (Table 1 and 2).CONCLUSIONS:This study in PTCL indicates that PET scans at the completion of therapy have a 50% false negative rate. These patients should not be assumed to have negative bone marrow involvement based solely on PET/CT scans. A bone marrow biopsy at the end of therapy is necessary in PTCL patients to confirm complete response.Table 1Bone Marrow InvolvementPre-Therapy PET Scan ImagingPET NegativePET PositiveTotal PatientsBone Marrow NegativeNANANABone Marrow Positive8816Total Patients8 (50%)8 (50%)16Abbreviations: NA, not applicable. The study defined that all patients had to have a positive bone marrow at baseline to be eligible for the study.Table 2Bone Marrow InvolvementPET NegativePET PositiveTotal PatientsBone Marrow Negative426 (37.5%)Bone Marrow Positive8210 (62.5%)Total Patients12 (75%)4 (25%)16Table 1 and 2. Involvement of bone marrow with peripheral T-cell lymphoma based on evaluation by PET scans versus bone marrow biopsy. DisclosuresMaurer:Kite Pharma: Research Funding.

Extracavitary/solid variant of primary effusion lymphoma presenting as a gastric mass

BackgroundPrimary effusion lymphoma (PEL) is a rare subtype of large B-cell lymphoma associated with human herpesvirus 8 (HHV8). It has the highest incidence in HIV-positive individuals. It often presents as a malignant pleural, peritoneal and/or pericardial effusion without a detectable solid mass. Most cases are co-infected with Epstein–Barr virus (EBV). Rare cases of HHV8-positive lymphoma with features similar to PEL can present as tumor masses and are considered to represent an extracavitary or solid variant of PEL. We report a case of EBV negative, extracavitary/solid variant of primary effusion lymphoma presenting as a gastric mass. Case presentationA 48-year-old man was admitted to an outside hospital with abdominal pain and weight loss. At the outside hospital, he was found to be HIV positive and have a 3×2cm gastric mass. He was subsequently diagnosed with ALK negative anaplastic large cell lymphoma by gastric biopsy. The patient was referred to Harbor-UCLA Medical Center for further management. Review of the outside slides and additional stains performed at our hospital revealed sheets of large anaplastic lymphoma cells that were positive for CD30, CD138, MUM1 and HHV8, focally weakly positive for CD3, and negative for other T- and B-cell markers and EBER, consistent with extracavitary/solid variant of primary effusion lymphoma. Interestingly, for the first time, cyclin D1 positivity was also demonstrated in PEL. ConclusionPrimary effusion lymphoma, particularly the extracavitary/solid variant, is very rare, and the diagnosis can be challenging. In some cases, when CD30 is uniformly positive, this lymphoma can be misdiagnosed as ALK negative anaplastic large cell lymphoma. This lymphoma can also aberrantly express T-cell markers as seen in this case, making diagnosis even more difficult. Awareness of the existence and the features of solid variant PEL and assessment for HHV8 infection are essential for correct diagnosis.

Expression of microRNA in ALK-negative anaplastic large cell lymphoma and CD30-positive peripheral T cell lymphoma, not otherwise specified

To study the role of microRNAs (miRNAs) in ALK-negative anaplastic large cell lymphoma and CD30 positive peripheral T cell lymphoma (not otherwise specified), and discuss the pathogenesis of miRNAs in ALK-negative anaplastic large cell lymphoma. Three cases of ALK-negative anaplastic large cell lymphoma of lymph node, 3 cases of CD30-positive peripheral T cell lymphoma (not otherwise specified) of lymph node and 3 cases of reactive hyperplasia of lymph node were detected by high flow microarray of miRNAs. The method of real-time quantitative polymerase chain reaction was further applied for 7 miRNAs in 15 cases of ALK-negatie anaplastic large cell lymphomas of lymph node and 15 cases of CD30-positive peripheral T cell lymphoma (not otherwise specified) of lymph node. The significant difference of 13 miRNAs was found between ALK-negative anaplastic large cell lymphoma and CD30 positive peripheral T cell lymphoma (not otherwise specified) (P < 0.05), of which the result of 5 miRNAs was consistent with miRNAs expression spectrum: miR-664b-5p, miR-1275, miR-4739, miR-4736 and miR-504-5p, the difference was statistically significant (P < 0.05). Compared with reactive hyperplasia of lymph nodes, miR-664b-5p, miR-1275 and miR-4739 were significantly under-expressed (P = 0.004, P = 0.021, P = 0.031) and miR-4736 and miR-504-5p were significantly over-expressed (P = 0.009, P = 0.007) in ALK negative anaplastic large cell lymphoma. MiR-664b-5p, miR-1275, miR-4739, miR-4736 and miR-504-5p may become an important indicator in the differentiation ALK-negative anaplastic large cell lymphoma from CD30-positive peripheral T cell lymphoma (not otherwise specified). MiR-4739, miR-4736 and miR-1275 may play important role in pathogenesis of negative-anaplastic large cell lymphoma by target genes: TNFRSF8 and TMOD1.

Çocuklarda Primer Kutanoz T- Hücreli Lenfoma: İki Olgu Sunumu

Primary cutaneous lymphomas in children are rare and constitute a heterogeneous group in regard to histological subtype, clinical course and prognosis. Here, we present the clinical characteristics and outcomes of two children with primary cutaneous lymphoma with different histopathologic subtypes. They had been diagnosed as a skin abscess initially but had not responded to systemic antibiotherapy and dressing. After a biopsy and metastatic work up, one patient was diagnosed as primary cutaneous peripheral T-cell lymphoma, unspecified, and the other as primary cutaneous CD30 positive ALK negative anaplastic large cell lymphoma.

The outcome of ALK positive and ALK negative anaplastic large cell lymphoma (ALCL) following DA-EPOCH.

8564 Background: Systemic anaplastic large cell lymphoma (ALCL) is a clinically and molecularly heterogeneous type of peripheral T-cell lymphoma (PTCL). It may be sub-divided into cases with or wit...

Primary pancreatic ALK negative anaplastic large cell lymphoma

Primary pancreatic ALK negative anaplastic large cell lymphoma

A case of ALK negative anaplastic large cell lymphoma with leukaemic manifestation, transformed from CD4 positive T-cell large granular lymphocytic leukaemia

A case of ALK negative anaplastic large cell lymphoma with leukaemic manifestation, transformed from CD4 positive T-cell large granular lymphocytic leukaemia