Eriko Ogusa

R-CHOP therapy alone in limited stage diffuse large B-cell lymphoma

Long‐term observation has identified a pattern of continuing relapse in limited stage diffuse large B‐cell lymphoma (DLBCL) treated by three cycles of R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) plus involved‐field irradiation. We retrospectively analysed 190 untreated patients with limited stage DLBCL treated by R‐CHOP alone. All the patients were scheduled to undergo primary therapy with six cycles of full‐dose R‐CHOP. Cases with a dose reduction of more than 20% were excluded from the study. Additional local irradiation was allowed in patients with partial response (PR). Five patients received additional local irradiation after PR at the end of the R‐CHOP therapy. The median observation period was 52 months. Median age at diagnosis was 63 years. The responses to therapy were 180 complete responses, eight PR, and two progression of disease (PD). The 5‐year progression‐free survival and 5‐year overall survival rates were 84% and 90%, respectively, both in plateau. During the observation period, 29 patients experienced PD. The progression sites were the primary sites in 15 patients, outside the primary sites in 10, and undetermined in four patients. These results suggest that the ‘standard’ strategy of three cycles of R‐CHOP followed by involved‐field radiotherapy for limited stage DLBCL could be effectively replaced by six cycles of R‐CHOP alone.

Absolute monocyte count in follicular lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

Elevated absolute monocyte counts (AMCs) have been reported to indicate poor prognosis for patients with lymphoproliferative disease, including those with follicular lymphoma (FL) receiving various treatments. We evaluated the prognostic impact of AMC in 150 consecutive FL patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Progression-free survival (PFS) did not differ significantly according to the AMC level. Univariate and multivariate analyses did not indicate a prognostic significance of AMC for PFS. Thus, the AMC is not a prognostic factor for FL patients treated with R-CHOP. However, immunochemotherapy might influence the prognostic impact of AMC.

Clinical features of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue

We newly diagnosed 131 patients with extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue lymphoma between 1998 and 2010. We retrospectively studied 124 patients for whom complete clinical data were available at presentation and who had minimally undergone tumour staging by physical examination, computed tomography (CT), bone marrow aspiration, and biopsy. A slight female predominance (men, 58; women, 66) was observed in the study population; the median age was 67 years. The primary locations at presentation were the stomach (38%), orbita (20%), lung (12%), intestinal tract (8%), thyroid gland (6%), others (14%), and unknown (2%). Seventy per cent of patients had localized disease. Of the 124 patients, 14 (11%) had lymph node involvement, and 5 (4%) had bone marrow involvement. Five (4%) patients had both lung and gastric involvement. The 5‐year overall survival rate for the 124 patients was 96.1%. The overall vital prognosis was excellent. Moreover, gastro‐intestinal fiberscopic examination is essential, especially in cases with lung involvement at presentation. Copyright

Lymphocyte recovery on day 100 after allogeneic hematopoietic stem cell transplant predicts non-relapse mortality in patients with acute leukemia or myelodysplastic syndrome

Abstract To clarify the clinical significance of lymphocyte recovery on day 100 after allogeneic hematopoietic stem cell transplant (allo-HSCT), we retrospectively studied 157 patients with hematologic malignancies who underwent allo-HSCT. An absolute lymphocyte count < 500/μL was defined as lymphocytopenia. There was a significant relationship between lymphocytopenia and advanced disease at allo-HSCT or corticosteroid administration within 100 days. Lymphocytopenia on day 100 (hazard ratio [HR]: 2.4; 95% confidence interval [CI]: 1.3–4.5; p = 0.006) and advanced disease at allo-HSCT (HR: 2.2; 95% CI: 1.3–3.9; p = 0.005) were prognostic factors for overall survival by multivariate analysis. Advanced disease was significantly associated with relapse (HR: 2.8; 95% CI: 1.5–5.4; p = 0.002), while lymphocytopenia was an independent predictor of non-relapse mortality (HR: 2.8; 95% CI: 1.1–6.8; p = 0.027). These results suggest that lymphocyte recovery on day 100 may be an important predictor of late complications in patients receiving allo-HSCT for hematologic malignancies.

Predictive value of risk assessment scores in patients with hematologic malignancies undergoing reduced-intensity conditioning allogeneic stem cell transplantation.

Reduced‐intensity conditioning allogeneic stem cell transplantation (RIC allo‐SCT) is associated with less toxicity and is used for older patients. We retrospectively studied the predictive value of two risk assessment scores, which were the hematopoietic cell transplantation‐specific comorbidity index (HCT‐CI) and the pre‐transplantation assessment of mortality (PAM) score, for assessing the outcome of RIC allo‐SCT. Seventy‐eight patients underwent transplantation between 2005 and 2013 at a single institution. RIC was performed with fludarabine and melphalan with/without total body irradiation. The 3‐year overall survival of patients with an HCT‐CI >3 was significantly worse than that of patients with an HCT‐CI 0–3 (31.6% vs. 59.6%, P = 0.020). Also, the 3‐year overall survival of patients with a PAM score >24 was significantly worse than that of those with a PAM score ≤24 (29.2% vs. 61.4%, P = 0.005). The present findings suggest that changing the cut‐off values of these risk assessment scores can improve prediction of outcomes in patients receiving RIC allo‐SCT with this conditioning regimen and we need validation by large‐scale study with other regimens. Am. J. Hematol. 89:E138–E141, 2014.

Prognostic index for relapsed acute leukemia after allogeneic stem cell transplant

Abstract We retrospectively studied patients who relapsed after allogeneic stem cell transplantation (SCT) to identify factors influencing outcomes. Of the 296 patients (196 with AML and 100 with ALL), 102 (34%) experienced relapse at a median of 222 days (range: 30–2,748) after SCT. Multivariable analysis showed that high disease risk (hazard risk [HR]: 1.95; 95% confidence interval [CI]: 1.17–3.24; p = 0.010), unrelated donor (HR: 1.76; 95% CI: 1.10–2.80; p = 0.018), and interval of < 180 days from SCT to relapse (HR: 2.10; 95% CI: 1.26–3.51; p = 0.004) were independent factors of 2-year post-relapse survival (PRS). These factors were used as a prognostic index for PRS. The 2-year PRS in patients of score 0, score 1, score 2, and score 3 was 38%, 19%, 3%, and 0%, respectively (p < 0.001). Our new prognostic index may be helpful for selecting the treatment for relapsed patients after SCT.

Human herpesvirus‐6 encephalopathy after hematopoietic stem cell transplantation and class I human leukocyte antigen

Human herpesvirus‐6 (HHV‐6) encephalopathy is a serious complication of allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Although reactivation of HHV‐6 is often observed after allo‐HSCT, encephalopathy only affects a few patients with HHV‐6 reactivation. Human leukocyte antigen (HLA) class I is expressed by most somatic cells, and a relationship between some class I alleles and neurological diseases has been reported. The HHV‐6 load at two, three, and four weeks after allo‐HSCT was examined. HHV‐6 encephalopathy was diagnosed from symptoms, results of cerebrospinal fluid examination, and magnetic resonance imaging findings. The relation between HHV‐6 reactivation or encephalopathy and the HLA class I status of the recipients was investigated. In 130 patients, 147 allo‐HSCT transplantation procedures were carried out. HHV‐6 reactivation and encephalopathy occurred in 56 and nine procedures, respectively. HLA mismatch (p = 0.008) and unrelated donor (p = 0.001) were associated with HHV‐6 reactivation, but not with HHV‐6 encephalopathy. HHV‐6 encephalopathy was more frequent in patients with HLA‐B*40:06 (p = 0.027). In addition, HLA‐A*26:01 and HLA‐B*40:06 were found to be associated with each other (p = 0.089), while HLA‐B*40:06 and HLA‐C*08:01 showed a significant association (p < 0.001). The HLA class I alleles of recipients may be associated with the occurrence of HHV‐6 encephalopathy after allo‐HSCT.

Recovery of natural killer cells and prognosis after cord blood transplantation

The relationship between immune reconstitution and the prognosis after cord blood transplantation is unclear. We investigated the influence of natural killer (NK) cell recovery on transplant outcomes. The maximum number of CD56+CD3- cells or CD57+CD16+ cells was determined to assess NK recovery. Although the high CD56+CD3- group and high CD57+CD16+ group showed significantly better overall survival (OS) than the low group on univariate analysis, the high CD57+CD16+ group was associated with better OS on multivariate analysis. These results suggest that CD57+CD16+ cell recovery is more closely related to the outcome after CBT than CD56+CD3- cell recovery.

Hyper-recovery of platelets after induction therapy is a predictor of relapse-free survival in acute myeloid leukemia.

Abstract We verified the association between standard clinical and laboratory variables and the risk of relapse in acute myeloid leukemia (AML), which led us to retrospectively examine the effect of regeneration of hematopoiesis in patients with newly diagnosed AML. We used data from 230 patients who obtained remission after cytarabine-based induction chemotherapy. Platelet counts ≥500 × 109/L and hemoglobin levels ≥9 g/dL on day 28 after treatment initiation were significantly associated with relapse-free survival (RFS) rate, conferring respective multivariate risk ratios of 0.38 (95% CI: 0.18–0.79) and 0.60 (95% CI: 0.40–0.89) for the occurrence of relapse or death. No disease relapse occurred in core binding factor leukemia patients whose platelet counts recovered ≥500 × 109/L at 28 days after therapy initiation. We conclude that regeneration of hematopoiesis, especially platelet hyper-recovery, after induction chemotherapy is a significant predictor of RFS in patients with AML.

Clinical manifestations of primary pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in Japanese population

We retrospectively analysed 16 cases of newly diagnosed pulmonary mucosa‐associated lymphoid tissue (MALT) lymphoma in the Japanese population. The disease was found on the basis of examination findings in 14 cases, and clinical manifestations in 2. According to the extensive staging procedure, four patients had concomitant gastric involvement. Primary treatment involved surgery alone in two patients; surgery followed by rituximab (R)‐containing chemotherapy in two; R‐containing chemotherapy alone in 11; and chemoradiotherapy without R in one. Over the median observation period of 28 months, disease progression was recorded in three patients, but all 16 patients were alive at the end of the observation period. One patient was treated with R alone and achieved partial remission; subsequent tentative surgery showed no evidence of residual lymphoma. It has been 72 months of progression‐free survival after the diagnosis. Primary pulmonary MALT lymphoma exhibited an indolent clinical course. R has potential as a therapeutic agent in patients with pulmonary MALT lymphoma. Copyright