Cyclophosphamide, Doxorubicin, Vincristine And Prednisolone Research Articles

(18)F-FDG PET in Patients with Primary Systemic Anaplastic Large Cell Lymphoma: Differential Features According to Expression of Anaplastic Lymphoma Kinase.

Primary systemic anaplastic large cell lymphoma (ALCL) is divided into two entities according to the expression of anaplastic lymphoma kinase (ALK). We investigated (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) findings in primary systemic ALCL according to ALK expression. Thirty-seven patients who had baseline PET before CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)-based chemotherapy were enrolled. Among them, patients who underwent interim and/or post-therapy PET were further investigated for the treatment response and survival analysis. Baseline PET was analyzed visually and semi-quantitatively using peakSUV, and interim and post-therapy PETs were visually analyzed. All cases were (18)F-FDG-avid on baseline PET. The peakSUV of ALK-positive ALCL (n = 16, 18.7 ± 10.5) was higher than that of ALK-negative ALCL (n = 21, 10.0 ± 4.9) (P = 0.006). In ALK-negative ALCL, complete response (CR) rate in negative-interim PET was higher than positive-interim PET (100% vs 37.5%, P = 0.02); however, there was no such difference in ALK-positive ALCL (100% vs 75%, P = 0.19). The 3-year progression-free survival (PFS) was not significantly different between ALK-positive and ALK-negative ALCL (72.7% vs 47.6%, P = 0.34). In ALK-negative ALCL, negative interim and post-therapy PET patients had better 3-year PFS than positive interim (83.3% vs 25.0%, P = 0.06) and post-therapy PET patients (70.0% vs 20.0%, P = 0.04). In contrast, ALK-positive ALCL had no such differences between PFS and PET results. On baseline PET, all cases showed (18)F-FDG-avidity, and ALK expression was related to higher (18)F-FDG uptake. ALK-positive patients tend to have better PFS than ALK-negative patients. Negative-interim PET was a good indicator of CR, and interim or post-therapy PET was helpful for predicting the prognosis only in the ALK-negative group.

A case of meningoencephalitis by the relapsing fever spirochaete Borrelia miyamotoi in Europe

On April 1 2012, a 70-year-old patient came to our clinic reporting slow cognitive processing, memory deficits, and a disturbed gait, all of which had gradually developed over several months and progressed during the last few weeks before the patient's initial visit. He did not report fever, and he had not been outside the country for several years. He had recently been treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), polychemotherapy, and rituximab (last dose on Aug 2, 2011) for a stage 4 diffuse large B cell lymphoma. His medical history also included Pneumocystis jirovecii pneumonia, unexplained chronic diarrhoea, a splenectomy, extensive tick exposure, and two tick bites in the summer and fall before onset of symptoms. On neurological examination there was a distinct bradyphrenia, and on cognitive assessment, the patient scored 26 of 30 points on the mini mental state examination. Vital signs were normal and body temperature was 36·4°C. Cranial MRI showed no abnormalities, but two lumbar punctures showed cerebrospinal fluid pleocytosis with raised protein values. The cause of this chronic meningitis was not identified by wide-ranging microbiological, pathological, and haematological diagnostic testing (appendix). A C6-immunofluorescence assay for Borrelia burgdorferi in serum, but not in cerebrospinal fluid, was weakly positive (index 1·8). However, a B burgdorferi IgG and IgM immunoblot were non-conclusive and negative, respectively. A B burgdorferi sl qPCR in cerebrospinal fluid was negative. Nonetheless, because of the absence of an alternative diagnosis and the progression of symptoms, on April 17, 2012, the patient was treated for a possible Lyme neuroborreliosis with once daily 2000 mg ceftriaxone intravenously for 2 weeks. During several weeks the patient fully recovered. At his last visit to the outpatient clinic in May, 2013, the patient did not have residual symptoms.

Serum level of soluble tumor necrosis factor receptor 2 is associated with the outcome of patients with diffuse large B‐cell lymphoma treated with the R‐CHOP regimen

Serum soluble tumor necrosis factor receptor 2 (sTNFR2) concentration predicted the clinical outcome of patients with aggressive non-Hodgkin's lymphoma including diffuse large B-cell lymphoma (DLBCL) treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) in our previous study. However, after rituximab (R) was introduced in clinical practice, R-CHOP replaced CHOP as the standard therapy for DLBCL. In this study, we re-evaluated the prognostic significance of serum sTNFR2 in 154 patients with DLBCL treated with R-CHOP. Five-yr overall survival (5-yr OS) rates with sTNFR2 ≥20 ng/mL and <20 ng/mL were 29.2% and 83.3% (P < 0.0001), respectively, and the corresponding 5-yr progression-free survival (5-yr PFS) rates were 26.9% and 76.4% (P < 0.0001), respectively. A multivariate analysis revealed that serum sTNFR2 and complete remission (CR) were independent prognostic factors for both OS (CR: P < 0.0001, sTNFR2: P = 0.0001) and PFS (CR: P < 0.0001, sTNFR2: P = 0.0001). The prognosis of patients with poor risk groups according to the revised International Prognostic Index who also had high serum sTNFR2 was especially poor. Serum sTNFR2 might be a powerful prognostic factor for patients with DLBCL in the rituximab era.

A Case of Extramedullary Plasmablastic Plasmacytoma Successfully Treated Using a Combination of Thalidomide and Dexamethasone and a Review of the Medical Literature

A 56-year-old man developed epistaxis, hoarseness, and swelling of a finger in March 2010. On the basis of biopsies of the masses in the pharynx and finger, he was diagnosed with extramedullary plasmablastic plasmacytoma, with somewhat immature CD45(+), MPC-1(-), and CD49e(-). CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and VCAP (vincristine, cyclophosphamide, doxorubicin, and prednisolone) therapy was ineffective, but combination therapy with thalidomide and dexamethasone was highly effective. Thalidomide monotherapy successfully maintained partial remission for approximately 7 months. A mass appeared in the right neck in February 2011, and a biopsy confirmed recurrence. Changes to CD45 negativity and MPC-1 partial positivity were seen, while CD49e negativity persisted, suggesting that the plasmablastic plasmacytoma had reverted to a more immature state. Bortezomib therapy was started in March 2011 and was effective. However, during the second round of treatment, the patient developed acute lung injury, which was improved by steroid pulse therapy. After the discontinuation of bortezomib, the extramedullary mass increased rapidly, and the patient died of multiple organ failure. An autopsy showed that plasmablastic plasmacytomas had infiltrated into multiple organs. Extramedullary plasmacytomas and those that revert to an immature state are associated with a poor prognosis, so further treatment improvements are needed in the future.

Darbepoetin alfa administration in patients with non-Hodgkin lymphoma and chemotherapy-induced anemia receiving (±R)CHOP

IMPACT NHL was a multicenter, observational study in adults with non-Hodgkin lymphoma receiving CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy with or without rituximab. Erythropoietin-stimulating agent treatment was given according to routine clinical practice and physician preference. In a subanalysis, outcomes were evaluated in 207 patients who received darbepoetin alfa (DA). The most common reason (81%) for initiating DA was low/declining hemoglobin (Hb) concentration. Mean (±standard deviation) duration of DA exposure was 8.8 ± 6.9 weeks (mean number of doses, 5.1 ± 4.6). Overall, 23% of patients had chemotherapy and DA treatment synchronized more than 75% of the time. At the time of DA initiation, 67% of patients had Hb concentrations in the guideline-recommended range (9–11 g/dl). Of 89 patients with Hb concentrations <10 g/dl at DA initiation and still receiving DA 5 weeks later, 92% (Kaplan–Meier) achieved Hb concentrations 10–12 g/dl between week 5 and at the end of treatment.

Durable Local Disease Control and Survival in Patients with Limited-Stage Diffuse Large B-Cell Lymphoma Receiving Involved-Node Radiation Therapy Plus Short-Course R-CHOP or CHOP Chemotherapy: Involved-Node Versus Involved-Field Radiation Therapy

AbstractAbstract 3665 Background:Chemoradiotherapy is considered as one of standard treatment for limited-stage diffuse large B-cell lymphoma (DLBCL). Involved-node radiation therapy (IN-RT) is a newly defined concept for patients with early Hodgkin lymphoma. However, there are as yet few reports of applying the strategy to DLBCL and the optimal radiation treatment fields for patients with limited-stage DLBCL have not been well defined. We conducted a retrospective study to evaluate efficacy and long-term toxicities in limited-stage DLBCL patients receiving IN-RT or involved-field radiation therapy (IF-RT) plus short-course chemotherapy. Patients and Methods:Subjects were consecutive patients newly diagnosed as limited-stage DLBCL and receiving local radiation therapy after short-course CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or R-CHOP (rituximab-CHOP) chemotherapy in our institute from 1993 to 2010. Each patient underwent CT simulation for treatment planning and decided to receive either IN-RT or IF-RT regarding diagnostic imaging after chemotherapy including FDG-PET or PET-CT. The concept of IFRT included the whole initially involved lymph node regions according to the Ann Arbor staging diagram. IN-RT was defined as radiation therapy fields that encompass the initially involved lymph nodes exclusively and to encompass their initial volume with adequate margin less than 3 cm. Results:A total of 108 patients were identified, of which 70 patients received IF-RT. The median age was 62 years (range: 19 to 81). Twelve patients (11%) had bulky disease (≥ 5cm). Baseline patients’ characteristics were given in Table 1. There was no statistically difference in risk factors as defined by the stage-modified International Prognostic Index score (IPI) between the two groups (P= 0.25). Most patients (94%) received three courses of chemotherapy (range: 2 to 4). Median dose of radiation was 40Gy (range: 23.4 to 51.2). With a median follow-up of 5.5 years (range: 0.35–17), the 5-year overall survival rates were 94% (95%CI: 87 to 97) in all 108 patients, and 94% (95%CI: 79 to 99) and 94% (94%CI: 84 to 98), in the groups of IN-RT and IF-RT, respectively (P=0.76). Estimated 5-year overall survival rates in patients undergoing IF-RT plus CHOP or R-CHOP were 92% and 94%, respectively (P=0.65). Estimated 5-year overall survival rates in patients treated with IN-RT plus CHOP or R-CHOP were 88% and 100%, respectively (P=0.10). Four patients in the IF-RT group experienced relapses [median: 1.8 years after the start of therapy (range: 0.9 to 7.6)], on the other hand, no patient had relapse in the IN-RT group. Three out of the four patients had three adverse risk factors as defined by the stage-modified IPI. Two patients had the relapsed diseases outside radiation fields. Cumulative incidence of relapse at 5 year was 0% and 4.6% (95%CI: 1.2 to 12) in the patients receiving IN-RT and IF-RT, respectively (P= 0.13).During long-term follow-up, a total of nine patients (8%) developed solid cancer, including skin (n=2), lung (n=2), breast (n=1), gastric (n=2) and bladder (n=2). Seven of which occurred outside radiation fields. No patients developed secondary MDS/AML. Cumulative incidence of secondary malignancy at 5 year was 2.7% (95%CI: 0.20 to 12) and 9.5 % (95%CI: 3.3 to 19) in the groups of IN-RT and IF-RT, respectively, and the cumulative incidence at 10 year was estimated to be 22% (95%CI: 4.0 to 49) and 23% (95%CI: 4.4 to 51) in the groups of IN-RT and IF-RT, respectively. There was no statistically difference in the occurrence of secondary malignancy between the two treatment arms. (P=0.70). Conclusions:IN-RT with short-course CHOP or R-CHOP chemotherapy could be expected as good as IF-RT in terms of local disease control and could produce excellent survival rates. However, incidence of secondary malignancy in patients receiving IN-RT was not decreased compared to that of IF-RT and the incidence was estimated to have been gradually increased until after 10 years. Physicians might consider the development of follow-up programs for patients with DLBCL undergoing chemoradiotherapy. [Display omitted] [Display omitted] Overall survival according to types of irradiation. The 5-year overall survival rates in patients receiving involved-node (IN-RT) and involved-field radiation therapy (IF-RT) were 94% (95%CI: 79 to 99) and 94% (94%CI: 84 to 98), respectively (p=0.76). Disclosures:Kinoshita:Chugai Pharmaceutical Co., LTD.: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria.

P1-156 - Early Relapse is Associated with the High Serum Soluble Interleukin-2 Receptor Level after the Sixth Cycle of R-CHOP Chemotherapy in Patients with Advanced Diffuse Large B-Cell Lymphoma

ABSTRACT Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. The present study assessed retrospectively the clinical significance of the serum soluble interleukin-2 receptor (sIL-2R) level in patients with advanced DLBCL. Twenty-one patients (age; range, 56–87, median, 73-year old, 14 males/7 females) were newly diagnosed as having advanced DLBCL (stages III and IV) based on pathological findings of the biopsy specimen and by using computed tomography and positron emission tomography between 2006 and 2009. All the patients received 6–8 cycles of the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) (R-CHOP) or THP-COP (pirarubicin, cyclophosphamide, vincristine and prednisolone) (R-THP-COP) and attained complete response at the end of the treatment. The follow-up period ranged between 12 and 73 months with the median of 37 months. The serum sIL-2R levels (normal range, 144–518 U/ml) were determined at least before and after the second and the sixth cycles of the chemotherapy were carried out. Although all the patients reached complete remission, six patients experienced the disease relapse within 1 year from the initiation of the treatment. sIL-2R levels before the chemotherapy ranged from 416 to 21300 U/ml (median 2609 U/ml). sIL-2R levels after the second cycle of the chemotherapy ranged from 276 to 1980 U/ml (median 675 U/ml). sIL-2R levels after the sixth cycle of the chemotherapy ranged from 364 to 822 U/ml (median 548 U/ml). The early relapse was significantly associated with the high sIL-2R levels at the sixth cycle of the treatment, while the sIL-2R levels were low in the patients with the durable remission. sIL-2R levels at the disease onset or after the second cycle of the treatment were not correlated to the duration of the remission. Thus, the present study suggested that the sIL-2R levels after the sixth cycle of the chemotherapy might predict the early relapse in patients with advanced DLBCL.

Prolonged immunochemotherapy with rituximab, cytarabine and fludarabine added to cyclophosphamide, doxorubicin, vincristine and prednisolone and followed by rituximab maintenance in untreated elderly patients with mantle cell lymphoma: a prospective study by the Finnish Lymphoma Group

There is no consensus on treatment strategies for elderly patients with mantle cell lymphoma (MCL). In this prospective phase II study we investigated whether the poor outcome could be improved, with reasonable toxicity, by prolonging the immunochemotherapy. Ten cycles of alternating cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP)/cytarabine (AraC) with eight doses of rituximab (R) were given as induction. The potential synergism of intermediate-dose AraC and fludarabine was tested in cycles 6–8. Induction was followed by bimonthly rituximab maintenance for 2 years. The median age of the 60 included patients was 74 years, and the Mantle Cell Lymphoma International Prognostic Index (MIPI) was intermediate or high risk in 98% of the patients. The overall response rate was 95% (complete response/complete response unconfirmed 87%). The response of 11 patients improved with cycles 6–8 (R-fludarabine-AraC). Progression-free survival was 70% and overall survival 72% at 4 years, respectively. Treatment related mortality was 2%. Severe infections were rare, with only one grade 4 infection. More dose reductions were needed during fludarabine-containing courses as compared to R-AraC. In 20 patients a transient grade 4 neutropenia without severe infections was recorded during maintenance. In conclusion, elderly patients with MCL can be treated relatively intensively with acceptable toxicity.

An Unusual Pulmonary Mass With Mediastinal Invasion and Multiple Intrapulmonary Nodules in a 52-Year-Old Man

An Unusual Pulmonary Mass With Mediastinal Invasion and Multiple Intrapulmonary Nodules in a 52-Year-Old Man

Clinical characteristics and outcomes of primary bone lymphoma in Korea

BackgroundThis study evaluates the effectiveness of immunochemotherapy and radiation therapy in the treatment of patients with primary bone lymphoma (PBL).MethodsWe retrospectively reviewed the medical records of 33 patients with PBL who were treated at 6 medical centers in Korea from 1992 to 2010. Clinicopathological features and treatment outcomes were analyzed.ResultsThe median age of the patients participating in our study was 40 years. The most common sites of involvement were the pelvis (12.36%) and femur (11.33%). CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens were administered to 20 patients (61%), and R-CHOP (rituximab plus CHOP) was administered to the remaining 13 patients (39%). The overall response rate was 89% (complete response, 76%; partial response, 12%). The overall survival (OS) of patients with solitary bone lesions was longer than that of patients with multiple bone lesions (median OS: not reached vs. 166 months, respectively; P=0.089). Addition of rituximab to CHOP did not significantly affect either OS or progression-free survival (P=0.53 and P=0.23, respectively). Combining radiation therapy with chemotherapy also did not improve the OS or progression-free survival of patients with solitary bone lesions.ConclusionConventional cytotoxic chemotherapy remains an effective treatment option for patients with PBL. Additional benefits of supplementing chemotherapy with either rituximab or radiation therapy were not observed in this study. Further investigation is needed to characterize the role of immunochemotherapy in treating patients with PBL.

A case of successful management of HHV-8+, EBV+ germinotropic lymphoproliferative disorder (GLD)

Human herpesvirus 8-positive (HHV-8⁺) and Epstein-Barr virus-positive (EBV⁺) germinotropic lymphoproliferative disorder (GLD) is extremely rare and occurs most commonly in immunocompetent persons who are human immunodeficiency virus (HIV)-seronegative. It is also recognized as a favorable response to conventional chemotherapy. Here, we report a case of a 75-year-old man with an incidentally found mass in the neck, compatible with GLD, which was detected by positron emission tomography (PET). Computed tomography (CT) scan, PET, and bone marrow studies showed only the left neck mass and no evidence of metastasis. Excisional biopsy of the mass was performed. The patient received four courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. After these treatments, he remained disease-free for 19 months. To the best of our knowledge, only five cases of HHV-8⁺, EBV⁺ GLD have been documented. This is the first such case report in Asia.

Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial

Post-transplantation lymphoproliferative disorder (PTLD) develops in 1-10% of transplant recipients and can be Epstein-Barr virus (EBV) associated. To improve long-term efficacy after rituximab monotherapy and to avoid the toxic effects of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy seen in first-line treatment, we initiated a phase 2 trial to test whether the subsequent use of rituximab and CHOP would improve the outcome of patients with PTLD. In this international multicentre open-label phase 2 trial, treatment-naive adult solid-organ transplant recipients diagnosed with CD20-positive PTLD who had failed to respond to upfront immunosuppression reduction received four courses of rituximab (375 mg/m(2) intravenously) once a week followed by 4 weeks without treatment and four cycles of CHOP every 3 weeks. In case of disease progression during rituximab monotherapy, CHOP was started immediately. Supportive therapy with granulocyte-colony stimulating factor after chemotherapy was mandatory and antibiotic prophylaxis was recommended. The primary endpoint was treatment efficacy measured as response rates in all patients who completed treatment with rituximab and CHOP, per protocol, and response duration, in all patients who completed all planned therapy and responded. Secondary endpoints were frequency of infections, treatment-related mortality, and overall survival. This study is registered at ClinicalTrials.gov, number NCT01458548. 74 patients were enrolled between Dec 12, 2002 and May 5, 2008, of whom 70 patients were eligible to receive treatment. PTLD was of late type in 53 (76%) of 70 patients, monomorphic in 67 (96%) of 70, and histologically EBV associated in 29 (44%) of 66 cases. Four of 70 patients did not receive CHOP. 53 of 59 patients had a complete or partial response (90%, 95% CI 79-96), of which 40 (68%, 55-78) were complete responses. At data cutoff (June 1, 2011) median response duration in the 53 patients who had responded to treatment had not yet been reached (>79·1 months). The main adverse events were grade 3-4 leucopenia in 42 of 62 patients (68%, 55-78) and infections of grade 3-4 in 26 of 64 patients (41%, 29-53). Seven of 66 patients (11%, 5-21) had CHOP-associated treatment-related mortality. Median overall survival was 6·6 years (95% CI 2·8-10·4; n=70). Our results support the use of sequential immunochemotherapy with rituximab and CHOP in PTLD. F Hoffmann-La Roche, Amgen Germany, Chugaï France.

Primary effusion lymphoma in an HIV‐negative man

A 55-year-old Caucasian male with cryptogenic cirrhosis of the liver and refractory ascites was referred for consideration of a liver transplant. There was no previous history of opportunistic infections and serological screening for human immunodeficiency virus (HIV), hepatitis B and hepatitis C was negative. Immunoglobulin levels were normal and autoantibodies and tumour markers were not detected. A computed tomography (CT) scan showed hepatomegaly with irregular hepatic architecture, established varices and marked portal enteropathy with splenomegaly and ascites but no nodal enlargement. Ascitic fluid cytology showed abundant atypical cells with hyperchromatic nuclei and many apoptotic cells (top left), macrophages and mesothelial cells. Immunophenotyping was undertaken on ascitic and pleural fluid and cells typed as mature T cells with no excess of blasts or clonally-restricted B cells. These cells expressed CD45, HLA-DR, CD38 and CD7 but no other B, T or myeloid markers. Immunohistochemistry of these cells failed because of background staining and poor preservation of cellular architecture. DNA was extracted from the ascitic fluid and gene rearrangement studies by multiplex polymerase chain reaction confirmed a monoclonal IGH@ rearrangement with a polyclonal T-cell receptor pattern. Peritoneal biopsy proved inconclusive but immunohistochemical analysis of a subsequent ascitic fluid sample showed pleomorphic lymphoid cells with plasmacytoid features, positive for CD38 (top right), CD30, epithelial membrane antigen (EMA) and MUM1/IRF4. There was strong nuclear expression of human herpesvirus 8 (HHV8) latent protein (LANA; bottom left) and Epstein–Barr virus-encoded RNA (EBER; bottom right) by in situ hybridization. A diagnosis of primary effusion lymphoma (PEL) was made. PEL is a rare large B-cell neoplasm and, in the absence of immune suppression, is particularly unusual. Confirmation of B-cell clonality by immunophenotyping may be difficult as PEL usually lacks cytoplasmic and surface immunoglobulin. CD45, HLA-DR, CD30, CD38, Vs38c, CD138 and EMA are often demonstrable. Pan-B markers may not be expressed and there may be aberrant expression of T-cell markers, making it difficult to assign lineage. Immunoglobulin genes are usually clonally rearranged, as in this case. The nuclei of the neoplastic cells are universally positive for HHV8 LANA and this is useful in establishing a diagnosis. If the cytological features are poorly preserved, histochemical staining may fail. The patient was treated with dose-attenuated cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapy, but had a poor response and died within 6 months of presentation. Clinical outcomes remain poor for this disease although there are occasional reports of a response to immunomodulatory agents with chemotherapy.

High Ki67 Index and Bulky Disease Remain Significant Adverse Prognostic Factors in Patients with Diffuse Large B Cell Lymphoma before and after the Introduction of Rituximab

The aim of this study was to evaluate the impact of clinical variables and biologic features on response rate (RR), overall survival (OS) and progression-free survival (PFS) in 111 patients with de novo diffuse large B cell lymphoma (DLBCL). Fifty-three patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and 58 patients were treated with R-CHOP (rituximab + CHOP). The variables predictive of RR in the CHOP group were B symptoms, age, clinical stage, bone marrow involvement, bulky disease, International Prognostic Index (IPI) and Bcl-2; in the R-CHOP group, these variables were bulky disease, bone marrow involvement, IPI and Ki67 expression >80%. Multivariate analysis showed that in patients treated with CHOP, the independent prognostic factors associated with PFS were age, bulky disease, IPI and Bcl-2 and those associated with OS were performance status, clinical stage, IPI and bone marrow involvement. In contrast, in patients treated with R-CHOP, the variable shown by multivariate analysis to be an independent prognostic factor associated with PFS was bulky disease, whereas Ki67 expression >80% was associated with OS and PFS. Our data show that a high Ki67 expression and bulky disease could represent possible predictive factors of poor prognosis, which would help to identify a high-risk subgroup of newly diagnosed DLBCL.

Comparing the Outcomes of CHOP Chemotherapy Alone with Rituximab Plus CHOP for Hong Kong Chinese Patients with Diffuse Large B-Cell lymphoma

AbstractAbstract 4894 IntroductionDiffuse large B-cell lymphoma (DLBL) is the commonest type of lymphoma worldwide. The condition is the same in Hong Kong and it accounts for about 30–40% of lymphoma cases. CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) was used for treatment of DLBL for many years. Rituximab, a chimeric anti-CD20 monoclonal antibody was used for the treatment of DLBL for about 10 years. Previous studies have shown the better efficacy of rituximab plus CHOP over CHOP alone, including the remission rate, overall and event-free survival. No previous study compared the efficacy of rituximab plus CHOP with CHOP alone in Hong Kong Chinese.We conducted a study to compare the outcomes of CHOP chemotherapy alone with rituximab plus CHOP in a local hospital in Hong Kong. MethodIt was a retrospective study from January 1999 to December 2009. Hong Kong Chinese patients with newly diagnosed diffuse large B-cell lymphoma were recruited in the study. They were divided into two groups. One group of patients was given CHOP chemotherapy and the other group was given rituximab plus CHOP. The remission rate, overall survival and event-free survival were compared in the two groups. Results62 patients were recruited in the study. Twenty-nine patients with median age of 55 (range 23–77) were given CHOP chemotherapy alone. Thirty-two patients with a median age of 53 (range 20–75) were given rituximab plus CHOP. The baseline characteristics were similar in both groups. There were 41% of male patients in each group. IPI (international prognostic index) score as well as the proportion of patients at stage III and IV disease were similar in both groups.The complete remission rate was 38% in CHOP alone group and 78% in rituximab plus CHOP group (p=0.002, Fisher's exact test).The 3-year overall survival rate was 47% in CHOP group and 74% in rituximab plus CHOP group (p=0.043). The 3-year event-free survival was also better in the rituximab plus CHOP group (p=0.026). 19 events (including relapse, progression and death) were observed in the CHOP alone group and 8 events were observed in the rituximab plus chemotherapy group.The side effects profile was similar in both groups and the rate of infection is comparable in both arms. ConclusionThis study has shown that the use of rituximab plus CHOP was better than CHOP alone in Hong Kong Chinese patients with newly diagnosed diffuse large B-cell lymphoma. The complete remission rate, overall survival and event-free survival were significantly higher in the rituximab plus chemotherapy group. Disclosures:No relevant conflicts of interest to declare.

Randomized phase II study of concurrent and sequential combinations of rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy in untreated indolent B‐cell non‐Hodgkin lymphoma: 7‐year follow‐up results

Rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) is one of the most frequently applied initial treatments for indolent B-cell non-Hodgkin lymphoma (B-NHL); however, information on its long-term outcome is limited. Untreated patients in the concurrent arm (Arm C) received six R (375 mg/m(2) ) treatments, 2 days prior to each cycle of CHOP, and patients in the sequential arm (Arm S) received 6 weekly R (375 mg/m(2) ) treatments following six cycles of CHOP. Sixty-nine patients were randomized but two patients were withdrawn before receiving the protocol treatment. Sixty-five patients (94%) had follicular lymphoma, and 37 (55%) were at low risk, 23 (34%) at intermediate risk and seven (10%) at high risk according to the Follicular Lymphoma International Prognostic Index. We previously reported that the overall response rate (ORR) in Arm C and in Arm S was 94% and 97%, respectively. The median progression-free survival (PFS)/7-year PFS rate in Arm C, Arm S and all 67 assessable patients was 2.4 years/23% (95% confidence interval [CI], 9-40%), 3.8 years/41% (95% CI, 23-57%) and 2.8 years/32% (95% CI, 20-45%), respectively. There was no significant difference between the two arms (P = 0.107). The overall survival (OS) of the 67 patients was 95% at 7 years. In conclusion, R-CHOP is a highly effective initial treatment for untreated indolent B-NHL in terms of ORR and OS; however, its long-term PFS is not good enough either in concurrent or sequential combination, warranting further investigations on post-remission therapy.

A case of anaplastic large cell lymphoma, ALK positive, primary presented in the skin and relapsed with systemic involvement and leukocytosis after years of follow-up period

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is one disease form of primary cutaneous T cell lymphoma (CTCL) that presents diffuse infiltration of large CD30 positive tumor cells. Its clinical course is usually favorable, with a 10-year disease-related survival of approximately 90% [1]. Unlike systemic anaplastic large cell lymphoma (ALCL), C-ALCL usually does not have translocations involving the anaplastic lymphoma kinase (ALK) gene. We report a case of ALK positive C-ALCL previously reported at the time of diagnosis [2] who developed systemic relapse with leukocytosis after years of the clinical course. A 54-year-old female first presented with progressive subcutaneous nodule on her left forehead. Excisional biopsy of the lesion revealed diffuse infiltration of anaplastic large lymphoma cells expressing CD30 and ALK, but in the previous report of this case at diagnosis, nucleophosmin (NPM)-ALK was not detected by reverse transcription-polymerase chain reaction (RT-PCR) [2]. She repeated local skin relapse thereafter, but was successfully treated by total excision or electron beam irradiation each time. Lymph node involvement occurred approximately two and a half years after her first presentation. By six courses of standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy, she achieved complete response (CR). After three years of another follow-up period, she presented repetitive vomiting after digestion and was admitted to our hospital. The laboratory data showed leukocytosis with atypical lymphocytes in the peripheral blood, thrombocytopenia, hyperbilirubinemia, and elevated serum inflammatory markers including C-reactive protein and soluble interleukin-2 receptor. Computed tomography (CT) revealed lymphadenopathy in the mediastinum and the abdomen, and hepatosplenomegaly and ascites that have not been evident one month before. Bone marrow biopsy revealed marked fibrosis. Flow cytometry of the peripheral blood detected CD30 and CD4 positive T cell population, which corresponded to the atypical lymphocytes initially involving the skin lesions, and she was diagnosed with relapse of ALCL. The cytogenetic analysis of the peripheral blood cells revealed a complex abnormal karyotype including t(2;5)(p23;q35), which is a typical chromosomal translocation resulting in the formation of the NPM-ALK gene often found in ALCL. Although temporary partial response (PR) was obtained after two courses of modified ESHAP therapy (methylprednisolone, etoposide, high dose cytarabine, and carboplatin), rapid tumor regrowth was evident after each course of chemotherapy. The disease became refractory after that, and the patient died five months after the systemic relapse. This case was previously reported as NPM-ALK fusion negative by RT-PCR. However, at the time of relapse, the peripheral blood cells revealed a complex abnormal karyotype including t(2;5)(p23;q35) suggesting NPM-ALK fusion. To obtain further information on the breakpoint of this translocation, fluorescent in situ hybridization (FISH) analysis using probes on the both sides of ALK gene at 2p23 [Vysis LSI ALK Dual Color Break Apart Rearrangement Probe (Abbott Molecular Inc., Illinois, USA)] was performed and revealed 0 breaks per 200 tested cells at M. Hosoi M. Ichikawa Y. Imai M. Kurokawa (&) Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan e-mail: kurokawa-tky@umin.ac.jp

Assessment of combination treatment with gemcitabine, cisplatin, and methylprednisolone (Gem-P) in the management of non-Hodgkin T-cell lymphoma.

8052 Background: T-cell lymphoma is rare and generally confers a poorer prognosis compared to B-cell lymphoma but traditionally receive CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). We investigated the feasibility of a gemcitabine-based regimen. Methods: Between 2000 to 2009, 29 consecutive patients who received Gem-P were identified through our clinical database. Treatment regimen: gemcitabine 1,000 mg/m2 D1, 8, 15 with cisplatin 100 mg/m2 D15 and methylprednisolone 1,000 mg D1-5 of each 28-day cycle. Cisplatin was substituted with oxaliplatin in patients with tinnitus or carboplatin where there was impaired renal function. Two patients also received combination rituximab. Assessment endpoint was response rate. Results: Median age at presentation was 53 years (range 17–72). M:F = 17:12. Stage I 5/29 (17%), stage II 2/29 (7%), stage III 10/29 (35%), stage IV 12/29 (41%). Subtypes included angioimmunoblastic (10), anaplastic large cell (6) [ALK-1 -ve (5), ALK-1 +ve (1)], peripheral T-cell not otherwise specified (6), NK/T-cell (3), adult T-cell leukemia/ lymphoma (2), mycosis fungoides (1), and enteropathy type (1). Patients received between one to six cycles of treatment. Average number of cycles received was 2.2. Overall radiological responses (complete response [CR] and partial response [PR]) were found in 21/29 patients (73%; 95% CI: 53-87%). Objective response rate in first line therapy was 80%. 10/11 of the patients who attained CR had stage III or IV disease. In addition, three patients achieved repeat objective response (1CR, 2PR) when rechallenged at relapse after 6 months or more. Overall grade 3/4 neutropenia and thrombocytopenia rates were 41.4% and 55.2% respectively. Conclusions: Gem-P achieved response both as initial treatment or salvage therapy after multiple line relapse. Prospective randomized trials will be needed to confirm its benefit in this distinct subgroup. Response n= 29 Overall (%) First line Second line Third line Fifth-sixth line CR 11/29 (38) 4/10 (40) 4/9 (45) 2/8 (24) 1/2 (50) PR 10/29 (35) 4/10 (40) 2/9 (22) 3/8 (38) 1/2 (50) Stable 1/29 (3) — 1/9 (11) — — Progressive 7/29 (24) 2/10 (20) 2/9 (22) 3/8 (38) — Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche

Results of immuno-chemotherapeutic treatment of patients with diffuse large B-cell lymphoma

Treatment with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) has been considered as the standard therapy for diffuse large B-cell lymphoma (DLBCL) for more than 20 years. CHOP treatment in combination with targeted immunotherapy, rituximab (R-CHOP), resulted in significant improvements in the treatment of this group of patients. In this study, efficacy of R-CHOP and R-CHOP-like treatments was analysed. Results were compared to the data of historical patients only receiving CHOP treatment or CHOP-like treatment. Between September 2002 and April 2005, 140 newly diagnosed, untreated DLBCL patients started to receive R-CHOP treatment in a single centre. The eligibility criteria included advanced stage (clinical stages III-IV), or large tumour size (>7 cm) and/or symptom B or extranodal manifestation in the case of clinical stages I-II. The results were compared to the data of 130 patients only receiving CHOP treatment in the past. In the patients receiving R-CHOP, the therapeutic outcomes were superior for all parameters. During an average follow-up period of 44 or 52 months, the overall remission rate was 73.6% in the R-CHOP group in comparison with 47.7% in the CHOP group. The 5-year overall survival was 68.6% vs. 41.0% (RR: 0.4293, CI: 0.2963-0.6221; p < 0.0001), the event-free survival was 59.8% vs. 33.5% (RR: 0.5038, CI: 0.3606-0.7038; p < 0.0001) and the progression-free survival was 64.4% vs. 37.6% (RR: 0.4915, CI: 0.3442-0.7019; p < 0.0001). Since prognostic parameters were more favourable in the R-CHOP group, patient groups were also compared using the International Prognostic Index score. Again, significant differences were revealed by the subgroup analyses. The 5-year overall survival was 74.4% vs. 47.9% (RR: 0.4475, CI: 0.2418-0.8285; p = 0.0084) and 52.0% vs. 28.8% (RR: 0.4989, CI: 0.3098-0.8035; p = 0.003) in the group with good prognosis and in the group with poor prognosis, respectively. In the group with very good prognosis, the statistical difference between the two groups in terms of the 5-year survival parameters remained undetectable as a result of the already very high therapeutic effect and low case number (OS and EFS: CHOP: 100% and 62.5% vs. R-CHOP: 90.9% and 87.0%; p = 0.3873 and p = 0.1702). Combining the standard CHOP treatment with rituximab resulted in a significant improvement of the therapeutic outcomes irrespective of the prognostic grouping. The data are comparable with those reported in the international literature.

Monotherapy with Anti-CD20 Monoclonal Antibody in a Heart Transplant Recipient with Sick Sinus Syndrome and Posttransplantation Lymphoproliferative Disorder: A Case Report

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with an incidence of 0.8% to 20% in heart transplant (HTx) recipients, and standard treatment may be too toxic in some cases. Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies and has been demonstrated effective in combination with chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). Cardiotoxicity with CHOP remains a major concern for treating HTx recipients with PTLD, however. We present a case of an HTx recipient with sick sinus syndrome and PTLD who was successfully treated with rituximab alone, avoiding the cardiotoxicity of CHOP. The cardiotoxicity induced by CHOP should be kept in mind in HTx recipients with PTLD, especially when there is an existing heart problem in such recipients. Monotherapy with rituximab can be considered a safe choice.