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The prognosis of therapy-related myelodysplastic syndrome and acute leukemia (t-MDS/AL) remains poor. We retrospectively analyzed the data of 47 patients (31 AL and 16 MDS) who were treated at our institute. Thirty-three patients received disease-adapted chemotherapy, with a response rate of 73%, while 14 received no interventions due to an indolent course, such as MDS. The median follow-up of surviving patients was 1.9 years (range 0.1-10.5) after the diagnosis of t-MDS/AL, and the estimated 3-year overall survival (OS) for all patients was 55%. Twenty-seven patients underwent allogeneic hematopoietic stem cell transplantation (HCT), and the 3-year non-relapse mortality was 17%. Twenty patients did not undergo HCT due to various reasons including advanced age or comorbidities. The 3-year OS was better in patients who received HCT than in those who did not (71 vs. 31%; p = 0.018). A multivariate analysis revealed that HCT was associated with a better OS. Although this study has several limitations, including a potential selection bias due to the retrospective nature of the analysis and a small number of patients, the results show that modern HCT may be useful for inducing long-term survival in a fraction of patients suffering from t-MDS/AL. The present findings warrant future prospective studies.

Background Information on the clinical behavior of the recently proposed primary duodenal follicular lymphoma (DFL) is limited. Patients and methods Demographic data, signs, symptoms, disease stage, and treatment of the patients diagnosed in National Cancer Center Hospital from 1999 to 2007 were collected and analyzed. Results Twenty-seven patients were studied. Nineteen patients were asymptomatic at the time of diagnosis. Twenty patients had stage I disease. The histological grade was 1 or 2 in 26 patients. IgH/BCL2 fusion was shown in 20 of the examined 24 cases (83%). Fourteen patients received therapy upon diagnosis (local radiotherapy in 2 patients and chemotherapy in 12 including rituximab therapy), their response rate was 85%, and the estimated progression-free survival (PFS) rate at 3 years was 70%. One patient developed histological transformation. The other 13 patients were followed up; their estimated PFS rate at 3 years was 74%. Five among six cases responded to treatment even after progressive disease. All 27 patients have survived with a median follow-up time of 47.9 months. Conclusions The majority of primary DFL patients have a localized tumor of low-grade histology and are positive for t(14;18). Watchful waiting might be an alternative approach for its indolent course; however, further studies are warranted.

An increasing incidence of Pneumocystis jiroveci pneumonia (PCP) in patients with B-cell non-Hodgkin lymphoma (B-NHL) receiving rituximab treatment has been reported. We reviewed patients with B-NHL who underwent chemotherapy from 2004 to 2008 at our institution to identify risk factors for PCP development during and after chemotherapy. Among 297 patients with B-NHL, six developed PCP. Of 121 patients (41%) who received PCP prophylaxis with sulfamethoxazole–trimethoprim during chemotherapy, none developed PCP (0%), while among 176 patients (59%) who had no prophylaxis, six (3.4%) developed PCP at a median of 2 months (range: 1–3 months) after starting chemotherapy. Patients with CD4+ lymphocyte counts ≤200/mm3 before chemotherapy had a higher risk of developing PCP (p=0.045), while a history of rituximab treatment was not related to PCP. CD4+ lymphocyte counts ≤200/mm3 during and after chemotherapy were observed in 18.9% of patients.

The feasibility and efficacy of cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL (intermediate DLBCL/BL) have never been reported. The effects of adding rituximab to CODOX-M/IVAC have not been published either. Fifteen consecutive patients with a median age of 39 years were treated with modified CODOX-M/IVAC regimen (particularly, reducing the dose of methotrexate to 3 g/m(2)) with or without rituximab at our institution. Although all patients developed grade 4 neutropenia and grade 3/4 thrombocytopenia/anemia, 93% had febrile neutropenia, 60% showed transaminase elevation, and 40% had mucositis/stomatitis (all grade 3), there were no treatment-related deaths. Two of nine patients treated with rituximab developed biphasic late-onset neutropenia. Thirteen patients (87%) showed complete responses. The remaining two patients had refractory disease; one had presented with peritoneal dissemination and complex chromosomal abnormalities, while the other had double IGH-MYC and IGH-BCL2 translocations. The estimated 5-year overall and progression-free survival were 87% each, with a median follow-up of 74 months. In conclusion, our modified CODOX-M/IVAC regimen is well tolerated and highly effective in Japanese adult patients with BL and intermediate DLBCL/BL, warranting a larger study for confirmation.

Oncology emergency refers to critical conditions among complications of cancer itself and adverse events by anti-cancer treatments. In my opinion, it can be divided into two categories including emergency in a narrow sense, which needs hasty correspondence within at least several hours, and urgency, which demands speedy one within not hours but one day. Even though they are the identical condition, certain oncologic emergencies can be assigned to different categories such as emergency, urgency and others in terms of their time course and severity. Furthermore, cancer diagnosis can be triggered by diagnosis of oncology emergency, and therefore considered to be an important theme for all of health care providers. In some sense, patients' history and physical examination are more essential than laboratory and imaging tests in order to adequately divide into three categories mentioned above and take care of patients with oncology emergency. As a general internist as well as a medical oncologist, I would like to share its importance with all of you through dynamics from diagnosis to treatment of spinal cord compression and hypercalcemia as representative of oncologic emergency.

A 61-year-old man with hypertension had developed exertional dyspnea for 2 years. His symptom got worse with fever and wet cough 4months prior to admission (PTA), and inspiratory pain on his right chest 3 months PTA. He was suspected of having an atypical pneumonia or a tuberculosis on CT. Enhanced chest CT showed large mural defects in right main pulmonary artery, clearly delineated by contrast medium.He was diagnosed as having a pulmonary embolism and received anticoagulation therapy with heparin followed by warfarin. Despite 1 week of warfarin therapy, he remained symptomatic with no change in the pulmonary artery filling defects on repeated enhanced CT.Pulmonary artery sarcoma, or a metastatic tumor were suspected of by its time course and accompanying symptoms and signs of fever, secondary anemia, and weight loss. Increased uptake of FDG in the affected pulmonary artery indicated that pulmonary artery sarcoma was most likely.Aspiration cytology and needle biopsy through pulmonary artery catheter revealed malignant cells with results of CD31(-), CD34(-), D2-40(+),α-Actin(-), and AE1/AE3(+), consistent with pulmonary artery sarcoma which was not able to be specified further.It was out of operative indication because of distant metastasis in his lungs. Therefore, he received weekly Paclitaxel(45mg/m2) + Carboplatin(AUC 2)concurrent with TRT 60Gy/30Fr in order to mainly control intra-arterial mass. However, we discontinued it at 6courses because of neutropenia(Gr3) and development and progression of non-tuberculosis mycobacterium infection. He was also intolerable to pazopanib due to many side effects of increasing in the liver enzymes(Gr1), hypertension(Gr3), anorexia(Gr3), diarrhea(Gr3), nausea(Gr3) and NTM exacerbation. On the other hand, his primary and metastatic lesions have a tendency to decrease in size in comparison with one before chemotherapy. We will report this case with literature review in terms of diagnostic difficulty of pulmonary artery sarcoma.

Background: There are few seminars with workshop style mainly consisting of group work in multidisciplinary care. We established in Nara prefecture a novel seminar called MAHOLOBA (Medical And HOListic Oncology Brush-up Academy) and reported 1st workshop in 2013. Objective: To clarify relevant issues on chemotherapy and ensure needs of participants for this sort of workshop. Participants: Physicians, nurses and pharmacists engaging in cancer chemotherapy. Method: Cross-sectional study. Primary outcome: Identify relevant issues on chemotherapy by K-J (Kawakita Jiro) method in 4groups and determine priority among them by two dimensions plotting of significance and emergency. Secondary outcome: Obtain information by means of questionnaires concerning satisfaction level of participants toward this workshop and their hope to it from now on. Results: Forty-six health care providers participated in the workshop and were divided into 4groups. Common relevant issues on chemotherapy among those groups were the followings: measures for adverse events(4/4), regimen management(4/4), measures for exposure(3/4), human resources(3/4) and equipment(3/4). Thirty-six participants, among whom 10 had qualification as an expert and 20 worked for core hospitals, answered the questionnaires with the results of high level of satisfaction(36/36) and wish(30/36) for participation in the next workshop. Many participants hoped to obtain the executable and sustainable contents at their own institute and share information among multicenter or multidiscipline. Conclusion: We identified those issues on chemotherapy including adverse events, regimen management and measures for exposure. We observed high level of satisfaction toward the workshop with multicenter and multidiscipline and ensured the need for it. COI: We received financial support to hold this workshop from Ono Pharmaceutical Co., LTD in Japan.

We present three cases of intracranial hemorrhage with metastasis of gastric cancer to the bone/bone marrow. Case1: A 62-year-old man with history of distal gastrectomy 15 years ago was pointed out to have elevated ALP level and diffuse increased uptake of bone scintigraphy, which turned out to be a recurrence of diffuse metastases to bone and bone marrow confirmed by bone marrow biopsy. After partially successful treatment of chemotherapy with 6 cycles of TS-1 + CDDP, he developed an acute subdural hematoma, complicated by DIC. Craniotomy for removal of hematoma was performed. However, he was died of brain bleeding 12 months after diagnosis of recurrence. Case2: A 60-year-old man underwent subtotal gastrectomy 9 years ago. Similarly, diffuse bone and bone marrow metastasis was confirmed by bone marrow biopsy with trigger of elevated ALP level and diffuse increased uptake of bone scintigraphy. After chemotherapy with TS-1 + CDDP as 1st line and DTX as 2nd line was performed, he also developed and died of subdural hematoma with DIC 22months after diagnosis of recurrence. Case3: A 65-year-old woman with rheumatoid arthritis was pointed out to have low platelet and elevation of LDH and ALP in her regular visits. Endoscope examinations and imaging studies showed gastric cancer with multiple metastases to bone and bone marrow complicated by DIC. Although chemotherapy with TS-1 and blood transfusion was performed, she developed an acute subdural hematoma and received craniotomy for removal of hematoma. However she died of brain rebleeding 4 months after initial diagnosis. The following things are quite interesting in these 3 cases. 1) The former 2cases recurred with bone and bone marrow metastasis after long interval. 2) All cases developed bone and bone marrow metastasis complicated by fatal intracranial hemorrhage without obvious bleeding tendencies in other parts of body. We will discuss those issues with literature review.

Abstract 3087 Poster Board III-24 Objective To evaluate the efficacy and safety profile of an intensive induction and post-remission Cx for untreated patients (pts) with adult ALL and LBL, focusing on the long-term follow-up results. Feasibility and efficacy of autologous or allogeneic SCT were also assessed. Patients and Methods We enrolled pts with untreated adult ALL or LBL aged 15 to 69 years. The Cx regimen consisted of induction Cx (vincristine [VCR], cyclophosphamide [CPA], prednisone [PSL], doxorubicin [DXR], L-asparaginase plus intrathecal methotrexate [IT-MTX]) followed by two consolidation Cx regimens (Consolidation A, consisting of daunorubicin, cytosine arabinoside [Ara-C], vindesine [VDS], PSL plus IT-MTX; Consolidation B, consisting of CPA, Ara-C, 6-mercaptopurine [6-MP], VCR plus IT-MTX) with the prophylactic use of granulocyte colony-stimulating factor. Thereafter, interim maintenance Cx including 6-MP and MTX concurrent with CNS prophylaxis (IT-MTX), intensification Cx (VCR, DXR, PSL, CPA, Ara-C and 6-MP) and maintenance Cx (VDS, CPM, PSL, DXR, MTX and 6-MP) were sequentially performed for two years. For pts with 50 years or younger who achieved complete remission (CR) after induction Cx, allogeneic SCT for ALL from HLA-matched related donor and autologous SCT for LBL were to be considered. Primary endpoint was 5-year progression-free survival (PFS). Secondary endpoints included CR rate (%CR), overall survival (OS) and adverse events. Results Among 115 pts who were enrolled between 1994 and 1999, 108 eligible pts (median age, 33.5 years [15-69]) including 96 ALL and 12 LBL pts who received induction Cx were assessed. Seven pts were judged ineligible, including four histologically ineligible pts revealed by institutional or central review. Other major characteristics of the 108 eligible pts were as follows: 54 males (50%); T-cell phenotype, 23 pts (21%); Ph, 24 pts (22%); t(4;11), 2 pts (2%); B-symptom+, 38 pts (35%); PS 2/3, 24 pts (22%). Eighty-seven pts achieved CR (%CR 81%; 95% CI, 72-88%), while five patients (5%) died during induction Cx mainly due to infections. The median OS and the median PFS of the 108 eligible pts were 1.8 years (95% CI, 1.5-2.6 years) and 1.2 years (95% CI, 0.8-1.6 years), respectively. Their 5-year OS and 5-year PFS were 29% and 28%, respectively, with the median follow-up of the censored cases of 9.3 years (range, 2.0-12.3 years). The 5-year OS from the date of SCT of 31 pts who underwent allogeneic (n=19) or autologous (n=12) SCT during 1st CR was 51% (95% CI, 32-67%). Major non-hematologic toxicities of grade 3 or greater included infections (n=24, 21%), pulmonary complications (n=7, 6%) and diarrhea (n=7, 6%). As compared with the investigators' previous phase II trials for ALL and LBL, JCOG9402 improved PFS and OS as compared with JCOG8702 (MST, 1.2 years; 7-year OS, 15%; 7-year PFS, 13%) (Jpn J Clin Oncol 1999;29:340), but did not show improvement as compared with JCOG9004 (MST, 2.2 years; 5-year OS, 32%; 5-year PFS, 26%) (Cancer Sci 2007;98:1350). Conclusion Although the intensified induction and post-remission Cx was feasible and 28% of pts achieved long-term PFS, JCOG9402 failed to show improvement in long-term follow-up results as compared with the investigators' latest historical control. To further improve the therapeutic outcomes of adult pts with ALL and LBL, novel strategies are warranted. Disclosures No relevant conflicts of interest to declare.

Background: The management for recurrent lymphoma after allogeneic hematopoietic stem cell transplantation (HSCT) is challenging and it is not clear concerning its outcomes. Since potent graft-versus-lymphoma (GVL) effect is observed in some patients (pts) with follicular lymphoma (FL), peripheral T-cell lymphoma (PTCL) or adult T-cell leukemia/lymphoma (ATL) after allogeneic HSCT using reduced-intensity conditioning (Tanosaki et al, ASH 2006, BBMT2008;14:702), we hypothesized that it could also be exerted in relapsed patients. Hence, we retrospectively analyzed the outcomes among patients with lymphoma who relapsed after allogeneic HSCT. Patients and Methods: Between January 1999 and December 2007, 164 patients with refractory lymphoma, who were deemed incurable with standard or high-dose chemotherapy, underwent allogeneic HSCT in our single institution. Seventy-five pts remain in CR, 33 died associated with non-relapse mortality, 4 were lost follow-up, and 52 pts relapsed after the median of 71 days (range 1–1457), including 1 graft failure. Therefore, 51 pts were analyzed in this study. Results: Histological subtypes were diffuse large B-cell lymphoma (DLBCL) 13, ATL 12, lymphoblastic lymphoma 8, PTCL 7, FL 4, Hodgkin lymphoma (HL) 3, mantle cell lymphoma (MCL) 2, extranodal NK/T-cell lymphoma 2. Ten pts had an early relapse within 30 days, while 41 pts had a systemic (18 pts) or solitary relapse (23 pts) after the median of 98 days (range 33–1457). Relapse-oriented interventions included withdrawal of immunosuppressants (WIS), irradiation or surgical resection of localized lesion, donor lymphocyte infusion (DLI) and chemotherapy, which were used singly or in combination according to the clinical conditions; the breakdown and its outcomes were shown in Table. At the time of relapse, 46 pts (90%) had immunosuppressants, and WIS was first tried in 31 pts who didn’t have GVHD. Overall survival rate (OS) at 2 years after relapse in pts with relapse >day 30 and ≤day 30 was 37±8% and 0% (p Conclusions: These results suggested that some patients with chemo-refractory lymphoma with an immunogenic property could achieve a long durable disease-free survival after relapse without aggressive treatment modalities. Interventions and Outcomes Total Interventions Response WIS Ope/RT DLI Chemo CR (CCR)* PR NC/PD *CCR; continuous complete remission after relapse. Relapse >Day 30 Solitary 23 10 12 2 1 10 (5) 0 11 Systemic 18 15 0 1 1 6 (4) 1 11 Relapse ≤ Day 30 10 6 0 2 2 0 (0) 1 9 Total 51 31 12 5 4 16 (9) 2 31

Background: Ranimustine (MCNU), a derivative of nitrosourea that was developed in Japan, shows good penetration into cerebrospinal fluid and might be expected to decrease CNS relapse of lymphoid malignancies when used before transplantation (Takaue Y, et al. Cancer67:1830, 1991). However, its feasibility and efficacy have not been extensively analyzed in adult patients with lymphoma. Patients and Methods: We retrospectively evaluated an MCEC regimen which consisted of MCNU (200 mg/m2 on days -8 and -3), carboplatin (300 mg/m2 on days -7 through -4), etoposide (500 mg/m2 on days -6 through -4) and cyclophosphamide (50 mg/kg on days -3 and -2) in 68 patients with lymphoma (median age, 48 yr: range, 20–65 yr) who underwent autologous peripheral blood stem cell transplantation (PBSCT) at our institution between January 1999 and February 2008. The diagnosis included diffuse large B-cell lymphoma (n=32), T-cell lymphoma (12), Hodgkin lymphoma (9), follicular lymphoma (14), including 6 transformants, and intravascular lymphoma (1). The median time from diagnosis to PBSCT was 20 months (4–198 mo), and the median number of prior chemotherapy regimens was 3 (2–7). Sixty-six patients (97%) had ECOG PS< 2, 28 (41%) had prior XRT, 3 (4%) had bulky disease, 42 (62%) had stage III–IV disease, 19 (28%) had IPI at relapse of high (H) or high-intermediate (H-I), and one had IPS >4. The disease status at transplantation was 1st CR/PR in 10 (15%), ≥2nd CR/PR in 49 (72%), and NC/PD in 9 (13%). Results: The median number of days to neutrophils> 500 /μL and platelets> 20,000 /μL was 10 (8–19) and 10 (4–30), respectively. The platelet count did not decrease below 20,000 /μL in 9 patients. Grade (G) 4 non-hematological toxicities (CTCAE ver. 3.0) included elevated transaminase (1), hyponatremia of 116 mEq/L (1) and hypokalemia of 2.3 mEq/L (1). GI and CNS toxicities consisted of mucositis (G3, n=10), diarrhea (G3, n=27) and seizure (G2, n=1). G1 interstitial pneumonitis was observed in 5 patients. There were no grade 4 cardiac, pulmonary or renal toxicities except for one patient who died of treatment-related multi-organ failure. The cumulative incidence of relapse at 2 yrs was 49 %. Of 33 relapses, 2 occurred newly in the CNS without any previous history. With a median follow-up of 24 months (3–80) after transplantation for surviving patients, the 2-year overall survival (OS) and progression-free survival (PFS) were 68% (95% CI 55–81%) and 50% (95% CI 38–63%), respectively. In univariate analyses, T-cell phenotype (P Conclusion: The results suggested that autologous PBSCT with the MCEC regimen is a feasible and effective treatment option for relapsed/refractory lymphoma.