Hideaki Kitahara

Prolonged lymphocytopenia after bendamustine therapy in patients with relapsed or refractory indolent B-cell and mantle cell lymphoma

Prolonged lymphocytopenia after bendamustine therapy in patients with relapsed or refractory indolent B-cell and mantle cell lymphoma

Influence of the watch and wait strategy on clinical outcomes of patients with follicular lymphoma in the rituximab era

We analyzed the effects of the initial approach to patients with follicular lymphoma (FL) on outcomes in order to investigate whether the watch and wait (WW) strategy is still an acceptable approach in the rituximab era. We retrospectively analyzed 348 patients who were initially diagnosed with FL between 2000 and 2012. We compared the clinical outcomes of the WW cohort and immediate treatment cohort. Among 348 patients (median age of 57xa0years, range: 19–85), 101 were initially managed with WW and 247 were immediately treated. The median follow-up duration was 75xa0months (range: 7–169). The estimated median time to treatment failure (TTF) in the treatment following WW cohort and immediate treatment cohort were 92xa0months (95xa0% CI, 60.1–NA) and 77xa0months (95xa0% CI, 65.1–107.6), respectively, which were not significantly different (Pu2009=u20090.272) . In a multivariate analysis, clinical stage was identified as a predictive factor of TTF (HR 1.19, 95xa0% CI, 1.03–1.38, Pu2009<u20090.05). Neither overall survival rate nor cumulative risk of transformation between the WW cohort and immediate treatment cohort was significant. The results of the present study suggested that the WW strategy is still an acceptable approach for selected FL patients in the rituximab era.

Clinicopathological characteristics of follicular lymphoma with peripheral blood involvement.

Abstract This study aimed to indicate patient outcomes and pathological characteristics of follicular lymphoma (FL) with peripheral blood (PB) involvement. Of 533 patients with FL, 56 (11%) had PB involvement. Of the patients treated with rituximab, 39 patients with PB involvement had significantly shorter progression-free survival than 107 patients with stage IV disease without PB involvement (p = 0.021), but the overall survival was not different (p = 0.804). The histopathology of the primary sites was usually nodal (95%) low-grade (86%) FL with IGH/BCL2 fusion (75%). Flow cytometric and immunohistochemical analyses revealed that the incidence of CD10 positivity was lower in the bone marrow (55% and 58%) and PB (41% and not available) than in the primary site (86% and 93%) (p = 0.004 and p = 0.0001, respectively). Therefore, even if small lymphoma cells in the bone marrow and PB are negative for CD10, FL cannot be ruled out.

Prognosis of patients with peripheral T cell lymphoma who achieve complete response after CHOP/CHOP-like chemotherapy without autologous stem cell transplantation as an initial treatment

Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy has been mostly applied to patients with untreated peripheral T cell lymphoma (PTCL). Because the long-term outcome of patients with PTCL, especially those achieving complete response (CR), has not been fully elucidated, we retrospectively analyzed 78 consecutive patients initially treated with CHOP/CHOP-like chemotherapy, without high-dose chemotherapy followed by autologous stem cell transplantation (HDC/auto-SCT). Median overall and progression-free survivals in all 78 patients were 44 and 17xa0months, respectively, with a median follow-up of 62xa0months. In the 53 patients achieving CR, the median relapse-free survival (RFS) was 21xa0months, and 2-, 3-, and 5-year RFSs were 46, 45, and 36%, respectively. Although our results showed an unfavorable outcome for PTCL as a whole, those who achieved CR following CHOP/CHOP-like chemotherapy did not always have a poor outcome without the consolidation of HDC/auto-SCT; in particular, 45% of the 65xa0years or younger patients were alive without disease at 5xa0years.

Clinical features and outcomes of 139 Japanese patients with Hodgkin lymphoma.

Hodgkin lymphoma (HL) is a rare subtype of malignant lymphoma in Japan, and there are few reports of HL in Japan in recent years. We retrospectively analyzed the clinical features of 139 patients with HL who were diagnosed and treated at our institution between 1997 and 2011. The median age at diagnosis was 34xa0years with 83 male. Of these patients, 83 (60xa0%) were early stage and 56 (40xa0%)xa0were advanced-stage. Seventy-three patients (88xa0%) with early stage disease received ABVd followed by irradiation. All of the 56 advanced-stage patients received chemotherapy, mainly ABVd. The 5-year progression-free survival (PFS) rates and overall survival rates were 90 and 94xa0% in patients with early stage disease, and 71 and 90xa0% in those with advanced-stage disease. The PFS of patients with advanced-stage disease was significantly lower than those with early stage (pxa0=xa00.014). In conclusion, the outcomes of Japanese patients with HL in recent years were not improved as compared with the results of previous reports. We confirmed that patients with advanced-stage disease have lower PFS than those with early stage disease. Prospective studies are needed to establish novel treatment strategies to improve the outcome of HL patients, especially those with advanced disease.

Histopathological Characteristics of Lymphomas in the Upper Aerodigestive Tract. A Single-Institute Study in Japan.

We analyzed the histopathological characteristics of lymphomas biopsied from the upper aerodigestive tract between 2000 and 2014 at the National Cancer Center Hospital in Japan. Of a total of 309 consecutive cases, the following incidences were observed: mature B-cell neoplasms, 77% (n = 239); mature T- and NK-cell neoplasms, 20% (n = 63); classical Hodgkin lymphomas, 0.7% (n = 2); and lymphoblastic lymphomas, 2% (n = 5). Lymphomas were most frequently (57%) detected in the oropharynx. The majority of cases (89%) were mature B-cell neoplasms (diffuse large B-cell lymphoma, 60%; follicular lymphoma, 10%), and 10% of cases were mature T-cell neoplasms. Six cases of plasma cell neoplasm (4 primary and 2 secondary involvement) and 2 cases of plasmablastic lymphoma in the upper aerodigestive tract were observed. Two out of 3 cases of extraosseous plasmacytoma with available biopsy material were positive for EBER1. All 3 patients received irradiation and achieved complete response; 1 had not relapsed after 17 months and the remaining 2 relapsed as plasma cell myeloma and solitary plasmacytoma of the bone. Of 47 extranodal NK/T-cell lymphoma, nasal-type cases in the upper aerodigestive tract, 38 (81%) were present in the sinonasal region and the remaining 9 (19%) were in the oropharynx (n = 4), nasopharynx (n = 3), and oral cavity (n = 2). In conclusion, since both primary lymphoma and secondary involvement of lymphoma are often diagnosed using biopsied materials from the upper aerodigestive tract, pathologists and hematologists should recognize the characteristics of lymphoma in this tissue.

Clinicopathological features of classical Hodgkin lymphoma in patients ≥40 years old, with special reference to composite cases

OBJECTIVEnClassical Hodgkin lymphoma shows a peak incidence at 15-35 years, and a second peak in elderly patients; however, pathological characteristics of elderly patients with classical Hodgkin lymphoma have not been analyzed enough.nnnMETHODSnIn a total of 154 patients with classical Hodgkin lymphoma, we analyzed the clinicopathological characteristics of classical Hodgkin lymphoma patients aged ≥ 40 years old, with special reference to the incidence, histopathology and outcome of patients with composite classical Hodgkin lymphoma.nnnRESULTSnOf 154 patients with classical Hodgkin lymphoma, 50 (32%) were ≥ 40 years old. The 5-year progression-free and overall survival rates were 59 and 86%, respectively. Thirty-eight patients (76%) had non-composite classical Hodgkin lymphoma, 10 patients (20%) had composite (6 simultaneous and 4 consecutive) classical Hodgkin lymphoma and B-cell non-Hodgkin lymphoma and 2 patients (4%) had methotrexate-associated classical Hodgkin lymphoma. Of 10 patients with composite classical Hodgkin lymphoma, composite lymphomas were detected throughout the staging procedure of the upper gastrointestinal tract or bone marrow in 4 patients. Fluorescence in situ hybridization revealed that the composite lymphomas of 4, 1 and 5 patients were related, unrelated and of unknown correlation status, respectively. The treatments after the diagnosis of a classical Hodgkin lymphoma component varied, and three patients died of lymphoma.nnnCONCLUSIONSnWe found that the incidence of composite classical Hodgkin lymphoma in patients ≥ 40 years old was 20%. Correct diagnosis and optimal treatment for patients with composite classical Hodgkin lymphoma and B-cell non-Hodgkin lymphoma is highly important in this patient population.

Classical Hodgkin lymphoma primary refractory to brentuximab vedotin, with transformation to CD30-positive diffuse large B-cell lymphoma.

Brentuximab vedotin (BV) is an antibody–drug conjugate that targets CD30. It is highly effective for relapsed/refractory classical Hodgkin lymphoma (CHL), and has become a promising treatment option for these patients; however, approximately 25xa0% of patients are refractory to BV. Until now, the clinicopathologic features of CHL refractory to BV have not been well understood. Here, we report a patient with relapsed CHL with an unfavorable outcome, whose disease was primary refractory to BV and was histologically diagnosed as a transformation from mixed cellularity CHL to CD30-positive diffuse large B-cell lymphoma (DLBCL). The transformation to DLBCL showing high tumor density and high proliferative activity (Ki67 index >90xa0%) was possibly related to the primary refractory to BV and an aggressive clinical course, although the lymphoma was diffusely and strongly positive for CD30.

Impact of the double expression of MYC and BCL2 on outcomes of localized primary gastric diffuse large B-cell lymphoma patients in the rituximab era.

Diffuse large B-cell lymphoma (DLBCL) is a common subtype of primary gastric lymphoma, accounting for 50–60% of cases.1 Prior to the rituximab era, a Japanese phase II trial evaluated three courses of cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP), followed by 40.5u2009Gy of involved field radiotherapy (IFRT) for localized (stage I, II1 based on the Lugano Staging System for Gastrointestinal Lymphoma2) primary gastric DLBCL (PG-DLBCL) and the study yielded good therapeutic results.3 Rituximab plus CHOP (R-CHOP) therapy has been shown to improve the prognosis of DLBCL patients over that of patients treated with CHOP.4, 5 The efficacy of three cycles of R-CHOP followed by IFRT for localized DLBCL was evaluated in a phase II trial by the Southwest Oncology Group and also showed favorable results.6 On the basis of these findings, a rituximab-containing regimen, particularly three cycles of R-CHOP followed by IFRT, is regarded as one of the standard therapies for localized DLBCL including PG-DLBCL. Recent studies demonstrated that the double rearrangement (double hit) of the MYC and BCL2 genes and the double expression of the MYC and BCL2 proteins were associated with a poor prognosis for patients with nodal DLBCL.7, 8, 9, 10 However, the clinical impact of the double expression of MYC and BCL2 on PG-DLBCL remains unknown. We retrospectively analyzed patients with localized PG-DLBCL who were initially treated with a rituximab-containing regimen, with a focus on the status of MYC and BCL2.

FUS-ERG gene fusion in isolated myeloid sarcoma showing uncommon clinical features

FUS-ERG gene fusion has not been reported in cases of myeloid sarcoma (MS), a subtype of acute myeloid leukemia involving extramedullary anatomic sites. Here, we report a case of a 48-year-old man with primary isolated MS of the anterior mediastinum, who later developed multiple extramedullary recurrences without bone marrow infiltration throughout the course. G-banding analysis of the cells in pericardial effusion at recurrence showed complex karyotypic abnormalities including t(16;21)(p11.2;q22). FUS break-apart fluorescent in situ hybridization analysis showed split signals in biopsy sections at initial diagnosis and recurrence. Reverse transcriptase polymerase chain reaction and direct sequencing demonstrated the presence of the FUS-ERG chimeric gene transcript. The patient underwent cord blood transplantation, but died of pneumonia on day 64. To our knowledge, this is the first report of isolated MS carrying FUS-ERG gene fusion. In future study, relationship between the fusion gene and uncommon clinical features should be investigated in isolated MS.