Cyclophosphamide, Doxorubicin, Vincristine, And Prednisolone Chemotherapy Research Articles

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with dismal outcomes. Standard CHOP (Cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy is still the most widely used regimen for front-line management. To explore new targeted drugs in PTCL, we conducted a phase 2, multi-center, non-randomized clinical trial, comparing the efficacy and safety of targeted agents combined with CHOP (CHOPX) with CHOP in newly diagnosed patients with PTCL. Methods: The primary outcome was complete response rate (CRR) at the end of treatment (EOT). Patients with newly diagnosed PTCL had enough tumor tissue for next generation sequencing (NGS) and were assigned to CHOPX and CHOP group based on investigators’ discretion. Patients in CHOPX group received intravenous cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1.4 mg/m2 (up to a maximum of 2 mg) on day 1, and oral prednisone 60 mg/m2 (up to a maximum of 100 mg) on day 1–5 every 21 days at the first cycle. X (i.e., targeted agent) was added from the second to sixth cycles as following, intravenous decitabine 10 mg/m2 on day -5 to -1 if with TP53 mutation. Subcutaneous azacytidine 100 mg on day −7 to −1 if with TET2/KMT2D mutation. Oral chidamide 20 mg on day1, 4, 8, 11 if with CREBBP/EP300 mutation. Oral lenalidomide 25 mg on day 1–10 if without above mutations. Patients in control group received standard CHOP regimen for 6 cycles. Analysis of efficacy and safety was of the intent-to-treat population. The study was registered with ClinicalTrials.gov, number NCT04480099. Results: Between 20 June 2020 and 22 September 2022, 108 patients were assessed for eligibility in the study. Ten patients met exclusion criteria and 2 patients withdrew informed consent before treatment. Forty-eight patients in the CHOPX group and 48 patients in the CHOP group were included into intent-to-treatment population. Baseline patient characteristics like age, gender, Ann Arbor stage, performance status, prognostic risk group was comparable between CHOPX and CHOP groups. The most common pathological subtypes were angioimmunoblastic T-cell lymphoma (67% vs. 60%), PTCL-not otherwise specified (17% vs. 21%), anaplastic T-cell lymphoma (6% vs. 8%) in the CHOPX and CHOP groups. As of 1 February 2023, 91 patients completed response evaluation at EOT. CRR in the CHOPX group was higher than the CHOP group (58% [25/43] vs. 33% [16/48]). The most common grade 3–4 hematological adverse events in CHOPX group were neutropenia (61%) and febrile neutropenia (27%). Conclusions: Preliminary analysis showed targeted agents combined with CHOP was effective and safe compared with standard CHOP in PTCL. Therapeutic strategy specifically towards molecular features may change current PTCL management in front-line setting. Keywords: combination therapies, molecular targeted therapies No conflicts of interests pertinent to the abstract.

Signet ring cell-like diffuse large B-cell lymphoma involving the breast: a case report

BackgroundDiffuse large B-cell lymphoma (DLBCL) with signet ring cell components is extremely rare. Here, we present a case of DLBCL with signet ring cell components involving the breast, which can be easily confused with invasive lobular carcinoma of the breast or metastatic signet ring cell carcinoma of gastrointestinal origin.Case presentationA 66-year-old woman presented with a painless mass in her left breast. Enhanced magnetic resonance imaging (MRI) of the breast revealed a 42 × 29 × 28 mm mass in the left breast. Histological examination revealed a diffuse or scattered arrangement of round cells mixed with signet ring-like cells. Immunohistochemically, the neoplastic cells were positive for PAX-5, CD79a, CD20, Bcl-6, and MUM-1 but and negative for cytokeratin, ER, PR, E-cadherin, and P120. The Ki-67 proliferation index was approximately 70%. Fluorescence in situ hybridisation (FISH) demonstrated non-rearrangement of Bcl-2, Bcl-6, and c-MYC genes. Immunohistochemistry and FISH examination confirmed the diagnosis of DLBCL. Subsequently, immunofluorescence showed both IgM and IgG deposits in the signet ring-like lymphocytes. After confirming the diagnosis, the patient received four courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy in a specialist hospital and achieved partial remission; however, she unfortunately died of secondary pneumocystis pneumonia infection 3 months later.ConclusionMalignant lymphoma with signet ring cell morphology is quite uncommon, and this variant can be a diagnostic pitfall. We emphasise that pathologists should consider lymphoma in the differential diagnosis of malignant breast tumours.

Comparison of R-CHOP with CHOP in Patients of Diffuse Large B Cell Lymphoma

Objective: Diffuse large B cell lymphoma (DLBCL) is a lymphoid B cells neoplasm with a diffuse pattern and high proliferation rate. Cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) was considered effective as other complicated regimens with more toxicity profile. Rituximab is a monoclonal antibody directed against CD20 positive B cell. It has good activity therapeutically in patients of DLBCL. It increases response rates and survivals when added to CHOP chemotherapy. Although R-CHOP is more effective but due to high cost of Rituximab it is usually not incorporated with chemotherapy in most of our patients and CHOP is still used extensively. Due to heterogeneity of disease and difference in ethnicity, there may be difference in outcomes of two regimens. This study will help us in tailoring our management plan that will result in better outcome of patients. Methods: 70 patients aged between 20-65 years having DLBCL were taken in this study. We rando-mized patients by lottery method into two groups. Group I received CHOP with dose of Cyclophosphamide 750mg/m2, Doxorubicin 50mg/m2, Vincristine 1.4 mg/m2 and prednisolone 40mg/m2.Chemotherapy was given on Day-1 while prednisolone was given for 5 days from Day-1 of chemotherapy. Group II received R- CHOP which includes same chemotherapy with same dosage. Rituximab was included in Group II with dose of Rituximab 375 mg /m2. Each cycle was given at three weeks interval. Response in terms of CR (Complete Response), PR (Partial Response), SD (Stable Disease) or PD (Progressive Disease) was evaluated as per leukemia network after 4 cycles of chemotherapy. The quantitative variables were calculated by taking mean and standard deviation. The response was assessed in percentage and frequencies and compared by applying chi square test. Results: Group I had 37.1% while Group II had 68.6% complete response with p value of 0.019. Partial response was 48.6% in Group I while 20.0% in Group II. 14.3% in Group I and 8.6% in Group II either had stable disease or progressive disease. Conclusions: R-CHOP has superior response rates as compared to CHOP, therefore, whenever possible Rituximab should be added as target therapy in chemotherapy. Key Words: Diffuse large B cell lymphoma, CHOP, R- CHOP How to Cite: Lodhi F.R, Zafar A, Khokhar M.A, Goraya AW, Ashraf S, Yaqub S. Comparison of R-CHOP with CHOP in patients of diffuse large B cell lymphoma. Esculapio.2020;16(04):79-82.

Report of two rare cases of adrenal incidentalomas with different origins: revisiting pathological and radiological findings with a short review of the literature

BackgroundAdrenal tumors can be detected incidentally in 4 to 8% of patients radiologically. Adenomas, pheochromocytomas, and adrenocortical carcinomas represent the most common tumors of the adrenal glands. Rare histopathological findings are uncommon. We aimed to report two rare primary adrenal tumors diagnosed initially as incidentalomas to identify clinical characteristics, management, and clinical outcomes after treatment.Case presentationThe first case was a 52-year-old man presented with an incidentally discovered locally advanced primary adrenal angiosarcoma. The patient was managed surgically with no adjuvant therapy. The patient was followed up for 3 years without evidence of local recurrence. The second case was a 63-year-old woman, presented with an incidentally discovered primary diffuse B-cell lymphoma of the left adrenal gland. She was treated by adrenalectomy. Later on, adjuvant six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy were given. After 6 months follow-up, the patient was alive and disease-free.ConclusionThe diagnosis of adrenal tumors increased nowadays because of the widespread use of imaging studies, though rare pathologies should be taken into consideration.

Breast implant-associated anaplastic large-cell lymphoma: first case detected in a Japanese breast cancer patient

This paper details the first breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) case detected in Japan. The patient, a 67-year-old Japanese woman, was diagnosed with left unilateral breast cancer 17 years ago. Induration and redness presented in the left breast, which had undergone immediate breast reconstructive surgery using a tissue expander, later replaced by a silicone breast implant (SBI). Breast ultrasound showed fluid collection around the SBI. Surgery was performed to remove the left breast implant and the fragmented capsule surrounding the implant. Postoperative pathological findings did not indicate malignancy. Nine months later, a contralateral axillary lymphadenopathy was observed, and an excisional biopsy of the axillary lymph node was performed. The patient was diagnosed with BIA-ALCL and successfully underwent adjuvant CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy.

PF324 RITUXIMAB DOSE ASSOCIATED WITH OVERALL SURVIVAL IN DIFFUSE LARGE B CELL LYMPHOMA

Background:The outcome of diffuse large B cell lymphoma (DLBCL) improved significantly, due to the addition of rituximab (R) to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. However, significant range of patients showed relapse or refractory to R‐CHOP, and the role of body surface area (BSA) or body mass index (BMI) to overall survival (OS) was not known or still controversial.Aims:We evaluated effects of rituximab dose, BSA or BMI on OS using National Health Information Database.Methods:This study included patients 5,332 patients who were diagnosed with DLBDL and received R‐CHOP as a frontline therapy between 2006 and 2014. The exclusion criteria were as follows;1) age <20 years 2) R‐CHOP was given less than 4 times or over 8 times 3) R‐CHOP 2 months after diagnosis 4) Interval between two consecutive R‐CHOP injection was over 60 days. We extracted age, sex, prescribed medication list, and date of death from NHID. Weight and height of patients who had national general health examination before 1st cycle of R‐CHOP was collected.Results:Median age was 58(20–92) years, and 57%(n = 3021) of them were male. Thirty‐eight % of patients (n = 2019) received R‐CHOP 4–5 times, and 62% (n = 3303), 6–8 times. Median dose of injected rituximab was total 7200(1,600–16,800) mg, and median mean dose of rituximab per each cycle was 600(400–1,000) mg. A total 2,523 patients (47.4%) were treated at medical institution in capital (Seoul) area. About 72% of patients (n = 3813) had national health examination before chemotherapy. Their median weight and height were 63(31–121) kg and 163(131–196) cm, respectively. Median BSA and BMI were 1.69m2 and 23.9 kg/m2.With median 66(24–144) months of follow up, estimated 5‐year and 10‐year overall survival was 37.1% and 25.6% respectively. Log‐rank test for 10‐year OS, age≤60 (vs age>60), female (vs male), 6–8 times of R‐CHOP injection (vs 4–5 times of R‐CHOP), total R dose≥7200 mg (vs <7200), mean R dose≥600 mg, and medical institution in Seoul (vs others) were associated OS, significantly (p < 0.05). However, total R dose did not affect OS in multivariate analysis (p = 0.152).Among 3813 patients who had national health examination before R‐CHOP, patients whose BSA <1.69m2 had worse OS than BSA≥1.69m2. But BMI did not differentiate OS.Summary/Conclusion:With 66 (24–144) months of median follow up, estimated OS at 5‐year and 10‐year of DLBCL patients were 37.1% and 26.5%, respectively. Mean rituximab dose ≥600 mg showed better OS than <600 mg. High BSA showed favorable OS, but BMI did not affected OS significantly. image

Effect of Everolimus on Epstein-Barr Virus-positive T Cell PTLD After CHOP Chemotherapy and Angiofibroma in Pediatric Tuberous Sclerosis Complex

A 15-year-old Japanese female with end-stage kidney disease, kidney cysts, and angiomyolipoma due to tuberous sclerosis complex (TSC) received an ABO-matched preemptive kidney transplantation from her father. Basiliximab induction therapy was done on days 0 and 4, and tacrolimus, mycophenolate mofetil, and methylprednisolone were administered. Six months later, cervical lymphadenopathy developed, and computed tomography revealed an abdominal mass. Epstein-Barr virus-positive T cell post-transplant lymphoproliferative disorders (PTLD) was diagnosed. The pathology showed a monomorphic type lymphoma, and the Ki-67 index, a cell proliferation marker, was above 90%. The patient received four courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy, and tacrolimus was switched to everolimus, an inhibitor of the mammalian target of rapamycin (mTOR) pathway. Everolimus acts not only as an immunosuppressant, but also has an anti-tumor effect which may inhibit lymphoma development and proliferation. Three years later, the patient has shown no sign of PTLD recurrence. Her kidney function remains good, and a pathological examination detected no sign of rejection. In addition, her facial angiofibroma has improved. Although this study is based only on a single case observed over a short period of time, we consider everolimus to be a possible option in the treatment of PTLD after CHOP chemotherapy, especially in patients with TSC.

CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial

SummaryBackgroundOutcomes with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like chemotherapy in peripheral T-cell lymphoma are poor. We investigated whether the regimen of gemcitabine, cisplatin, and methylprednisolone (GEM-P) was superior to CHOP as front-line therapy in previously untreated patients.MethodsWe did a phase 2, parallel-group, multicentre, open-label randomised trial in 47 hospitals: 46 in the UK and one in Australia. Participants were patients aged 18 years and older with bulky (tumour mass diameter >10 cm) stage I to stage IV disease (WHO performance status 0–3), previously untreated peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma, or hepatosplenic γδ T-cell lymphoma. We randomly assigned patients (1:1) stratified by subtype of peripheral T-cell lymphoma and international prognostic index to either CHOP (intravenous cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2 mg] on day 1, and oral prednisolone 100 mg on days 1–5) every 21 days for six cycles; or GEM-P (intravenous gemcitabine 1000 mg/m2 on days 1, 8, and 15, cisplatin 100 mg/m2 on day 15, and oral or intravenous methylprednisolone 1000 mg on days 1–5) every 28 days for four cycles. The primary endpoint was the proportion of patients with a CT-based complete response or unconfirmed complete response on completion of study chemotherapy, to detect a 20% superiority of GEM-P compared with CHOP, assessed in all patients who received at least one cycle of treatment and had an end-of-treatment CT scan or reported clinical progression as the reason for stopping trial treatment. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT01719835) and the European Clinical Trials Database (EudraCT 2011-004146-18).FindingsBetween June 18, 2012, and Nov 16, 2016, we randomly assigned 87 patients to treatment, 43 to CHOP and 44 to GEM-P. A planned unmasked review of efficacy data by the independent data monitoring committee in November, 2016, showed that the number of patients with a confirmed or unconfirmed complete response with GEM-P was non-significantly inferior compared with CHOP and the trial was closed early. At a median follow-up of 27·4 months (IQR 16·6–38·4), 23 patients (62%) of 37 assessable patients assigned to CHOP had achieved a complete response or unconfirmed complete response compared with 17 (46%) of 37 assigned to GEM-P (odds ratio 0·52, 95% CI 0·21–1·31; p=0·164). The most common adverse events of grade 3 or worse in both groups were neutropenia (17 [40%] with CHOP and nine [20%] with GEM-P), thrombocytopenia (4 [10%] with CHOP and 13 [30%] with GEM-P, and febrile neutropenia (12 [29%] with CHOP and 3 [7%] with GEM-P). Two patients (5%) died during the study, both in the GEM-P group, from lung infections.InterpretationThe number of patients with a complete response or unconfirmed complete response did not differ between the groups, indicating that GEM-P was not superior for this outcome. CHOP should therefore remain the reference regimen for previously untreated peripheral T-cell lymphoma.FundingBloodwise and the UK National Institute of Health Research.

Control of Constipation in Patients Receiving CHOP or CHOP-Like Chemotherapy Regimens for Non-Hodgkin's Lymphoma.

Management of constipation in patients receiving cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or CHOP-like chemotherapy regimens is important for prevention of paralytic ileus. We reported earlier that the laxative action of magnesium oxide is reversed by the concomitant use of antacids in cancer patients receiving opioid analgesics. Here, we assessed the prevalence of prophylactic laxative medication for the control of constipation in patients receiving CHOP or CHOP-like regimens for non-Hodgkin's lymphoma. Data obtained from 211 eligible patients were retrospectively analyzed. Almost all patients (99%) received anti-ulcer agents such as proton pump inhibitors and H2 receptor antagonists for the prophylaxis of gastric disorders associated with prednisolone. Prophylactic laxatives were prescribed in 86 patients (40.8%), in which magnesium oxide was used most predominantly (88.4%). However, magnesium oxide at doses of ≦2000 mg/d was not effective for prevention of constipation, although the compound totally inhibited the incidence of constipation at doses higher than 2000 mg/d. Therefore, it is important to avoid negative drug interaction between magnesium oxide and antacids in patients receiving CHOP chemotherapy.

Primary Cutaneous Extranodal Natural Killer/T-Cell Lymphoma Misdiagnosed as Peripheral T-Cell Lymphoma: The Importance of Consultation/Referral and Inclusion of EBV In Situ Hybridization for Diagnosis.

Primary cutaneous T-cell lymphomas (CTCL) are heterogenous extranodal non-Hodgkin lymphomas including a few distinct and provisional entities. Compared with the West, Asian populations have a relatively higher frequency of nonmycosis fungoides CTCL. Primary cutaneous extranodal natural killer/T-cell lymphoma (PC-ENKTL) is distinct from other CTCL by the presence of EBV association. In our recent retrospective Asian study of PC-ENKTL, we identified 5 cases initially misdiagnosed as various CTCL. We fully characterized these cases with immunohistochemistry, EBV in situ hybridization, and clonality study for T-cell receptor (TCR) γ-chain gene (TRG). The 5 patients included 3 males and 2 females with a median age of 45. All tumors were positive for EBER. Two cases were clonal for TRG gene rearrangement but without expression of βF1 or TCR-γ (TCR-silent T-cell origin), 1 tumor expressed TCR-γ (γδ T-cell origin), and the remaining 2 were polyclonal for TRG and negative for TCR expression (NK-cell origin). On the basis of the initial diagnoses (2 as peripheral T-cell lymphoma, unspecified, 2 as primary cutaneous anaplastic large-cell lymphoma, and 1 as subcutaneous panniculitis-like T-cell lymphoma), all patients received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy with additional radiotherapy in 3. All patients experienced persistent disease or relapse despite treatment in a mean duration of 8.8 months (range, 1 to 12 mo). PC-ENKTL is rare and aggressive. These cases strongly demonstrate the importance of consultation/referral to experienced hematopathologists and the inclusion of EBER in the initial diagnostic work-up for patients with nonmycosis fungoides CTCL to avoid erroneous diagnosis and subsequent inadequate treatment of the patients.

Chemotherapy continuity and incidence of febrile neutropenia with CHOP therapy in an outpatient setting.

The cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) regimen is considered to be a standard treatment for non-Hodgkin's lymphoma (NHL). Patients receiving CHOP chemotherapy often experience febrile neutropenia (FN) due to myelotoxicity. The proper management of FN is essential to guarantee a positive outcome of the NHL treatment. Therefore, the present study retrospectively examined chemotherapy continuity and the incidence of FN during CHOP therapy in an outpatient setting. The subjects were 136 patients who received CHOP chemotherapy between January 2012 and December 2014. A total of 31 patients unable to be treated in an outpatient setting were excluded from the study. Of the remaining 105 patients, 73 patients who did not require hospitalization during the chemotherapy treatment were included in the non-hospitalized group, and 32 patients who required hospitalization during chemotherapy treatment were included in the re-hospitalization group. The numbers of patients from these two groups who completed the planned treatment were 71 and 24, respectively (P<0.01). In addition, the duration of granulocyte-colony stimulating factor (G-CSF) treatment was 5.3±1.22 and 6.1±1.46 days, respectively (P<0.01). The numbers of patients experiencing FN in an outpatient setting were 14 and 19, respectively (P<0.01). During administration of primary prophylaxis with G-CSF, the incidence of FN was 21.0% (22/105) in cycle 1. In conclusion, the present study has revealed a requirement to educate patients about infection prevention prior to the first cycle of chemotherapy. Patients who require the administration of long- term G-CSF are at risk of unplanned re-hospitalization, and treating them with polyethylene glycol G-CSF to reduce the number of required injections should be considered as an option. Therefore, proper supportive therapy and management of infection are important to safely treat patients with CHOP in an outpatient setting.

Efficacy and Safety of Dose Attenuated CHOP Chemotherapy for Peripheral T-Cell Lymphoma in Elderly Patients

BackgroundPeripheral T-cell lymphoma (PTCL) is an uncommon disease entity that accounts for 10-15% of all non-Hodgkin lymphomas (NHL). Except for anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), the median age of patients ranges between 5th to 6th decades of life. Unfortunately, substantial numbers of the elderly patients are unable to tolerate full dose chemotherapy due to comorbidities or poor functional status. In this respect, we aimed to evaluate the efficacy and safety of the dose attenuated CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy in the elderly PTCL patients.MethodsWe analyzed data from patients with newly diagnosed PTCL aged over 65 years who presented to our institute between April 2001 and December 2014. NK/T cell lymphoma and mycosis fungoides were excluded from the study. Forty three patients were treated with the dose attenuated CHOP, which is a combination of cyclophosphamide (562.5 mg/m2 for 1 day, 25% dose reduction from full dose), doxorubicin (37.5 mg/m2 for 1 day, 25% dose reduction from full dose), vincristine (1.4 mg/m2 for 1 day) and prednisolone (50 mg bid for 5 days).ResultsThe median age was 72 years (range 65-86). Among the forty three patients, PTCL-not otherwise specified (NOS) accounted for 62.8% (n=27), AITL for 16.3% (n=7), ALK-negative ALCL for 11.6% (n=5), and enteropathy-associated T cell lymphoma (EATL) for 9.3% (n=4), respectively. Although 79.1% (n=34) of patients had good performance status (Eastern Cooperative Oncology Group (ECOG) performance status <2), 93.0% (n=40) were in advanced stage (> Ann Arbor stage II).The overall response rate (ORR) and complete response (CR) rate was 77.8% and 52.8%, respectively. With a median follow-up period of 50.1 months (range 16.4-83.8), the 5-year event-free survival (EFS) and overall survival (OS) was 31.1% and 45.1%. The 5-year relapse-free survival (RFS) in those who achieved CR was 57.4%. Involvement of extranodal sites (≥2) (P=0.007 and hazard ratio [HR] 1.76 for OS, P=0.026 and HR 2.09 for EFS) was an independent prognostic factor for both EFS and OS.The grade 3 and 4 adverse events were consistent with the expected toxic effects of CHOP chemotherapy. Grade 3 or 4 neutropenia and thrombocytopenia was observed in 71.4% and 19.0%, respectively. However, 45.2% experienced febrile neutropenia. In addition, twelve patients died from treatment-related toxicities. Another 10 died from progression of disease, and the other two from unknown causes.ConclusionDose attenuated CHOP with 25% dose reduction of cyclophosphamide and doxorubicin for elderly PTCL doesn't seem to diminish response or survival rates, which resulted in at least comparable efficacy outcomes to the prior reports (J Clin Oncol 2008;26:4124-4130). However, it is still associated with significant toxicities with high treatment-related mortalities. Novel treatment strategies for these vulnerable elderly patients are urgently needed. DisclosuresNo relevant conflicts of interest to declare.

Autologous peripheral blood stem cell mobilization following high-dose CHOP chemotherapy combined with rituximab in patients with NHL.

e18003 Background: The CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen is an efficient treatment of non-Hodgkin’s lymphoma (NHL). This study was aimed to assess the efficacy and toxicity of high-dose (HD) CHOP ± rituximab on autologous peripheral blood stem cell (APBSC) mobilization for the patients with NHL. In the meantime, factors affecting the collection of CD34+ cells were explored. Methods: 39 patients eligible for autologous stem cell transplantation (ASCT) were included in this retrospective study, 14 patients received HD CHOP combined with rituximab for APBSC mobilization and the others received HD CHOP regimen alone. Results: For all, the median number of CD34+ cell yield was 7.01×106/kg with 37 patients achieving to meet the target CD34+ cell harvest of ≥2.0×106/kg and 27 patients (69.2%) achieved the optimal collection≥5.0×106/kg. 26 of the patients underwent only one apheresis procedure with median CD34+ cell collection of 6.93×106/kg. The mobilization yield of CHO...

A Unique Composite Follicular Lymphoma and Mantle Cell Lymphoma With a Mixed Cell Pattern and Aggressive Course

There are a limited number of reports of composite follicular lymphoma (FL) and mantle cell lymphoma (MCL) in the literature, and all previous cases report that FL and MCL components are separated, even within a single lymph node. Here we report a case of a patient with a distinctive composite FL and MCL with a mixed cell pattern. A 34-year-old man presented with left supraclavicular lymphadenopathy for one month. The lymph node contained closely packed nodules of lymphocytes. Immunostaining and fluorescence in situ hybridization demonstrated the FL nature of the Bcl-2- and CD10-positive tumor cells, as well as the scattered cyclin D1-positive MCL tumor cells in the nodules. Double immunohistochemical staining showed an unusual mixed pattern of both types of tumor cells. The patient received a regimen of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy and achieved partial remission following four cycles of chemotherapy but relapsed 1 month after the last treatment and died of meninges involvement 8 months after the first presentation. To our knowledge, this is the first report of composite FL and MCL with a mixed pattern. A mixture of grade IIIb FL and MCL may explain the poor prognosis of the patient.

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.

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

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.

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.