Low-dose Granulocyte Colony-Stimulating Factor Overcomes Neutropenia in the Treatment of Non-Hodgkin’s Lymphoma with Higher Cost-Effectiveness

To facilitate more economical medical care, we carried out a prospective study of whether a THP-COP regimen (cyclophosphamide, pirarubicin, vincristine, and prednisolone) with low-dose granulocyte colony-stimulating factor (G-CSF) would effectively treat non-Hodgkin's lymphoma (NHL). From April 2003 through March 2004, we enrolled 19 consecutive patients with newly diagnosed NHL treated at our hospital. The patients were divided into young and elderly groups. Each patient underwent chemotherapy with 8 courses of a THP-COP regimen with a 50-microg dose of lenograstim. Age- and sex-matched historical control patients (n = 141) received NHL diagnoses between 1998 and 2003. Each patient in the control group underwent the same chemotherapy and received a 100-microg dose of lenograstim. The mean (+/-SD) total amounts of G-CSF per cycle of chemotherapy were 332 +/- 103 microg (young patients) and 345 +/- 128 microg (elderly patients) in the low-dose group and 594 +/- 439 microg (young) and 730 +/- 551 microg (elderly) in the control group. The duration of fever in 1 cycle of chemotherapy was 0.3 +/- 1.0 days (young) and 0.1 +/- 0.8 days (elderly) in the low-dose group and 0.5 +/- 1.3 days (young) and 0.8 +/- 2.0 days (elderly) in the control group. A THP-COP regimen with low-dose G-CSF could be administered to NHL patients with safety. Administration of a 50-microg dose of lenograstim is sufficient and recommended for the treatment of NHL.     

Treatment results of aggressive B non-Hodgkin's lymphoma in advanced age considering comorbidity

The aim of this retrospective single institution study was to investigate the long-term outcome of sequential chemotherapy (CHT) and radiotherapy (RT) in patients >/= 70 years old, considering the International Prognostic Index (IPI) for high-grade non-Hodgkin's lymphoma (NHL) and comorbidity. The study involved 106 patients aged 70 years and above, treated between 1986 and 1998, for diffuse large B-cell NHL (DLBCL); 57% had localized disease (stage I or II) and 43% had advanced disease (stage III or IV). All patients received four to six cycles of CHOP (cyclophosphamide, hydroxy-daunorubicin, oncovin, prednisone) CHT at 14-21 d intervals, followed in 69 cases by extended-field or involved-field RT. Complete response rate was 65%; overall survival probability at 5 years was 41% in all stages. Five-year survival was 62% in patients with localized and 12% in advanced disease. There were 3% treatment-related deaths. The 5-year survival rate was 70% in patients with IPI low risk, 46% with low-intermediate risk, 28% with high-intermediate risk and 0% with high risk. Patients with cardiac problems and advanced disease were more susceptible to treatment-related toxicity. Patients with hypertension showed a high rate of vinca alkaloid-associated polyneuropathy. Most patients with localized DLBCL achieved long-term remission after CHT and RT regimens despite advanced age and frequent comorbidities. Advanced disease increased the risk for treatment-related complications and efficacy of treatment seemed limited.     

Do cytogenetic abnormalities precede morphologic abnormalities in a developing malignant condition?

Cytogenetic evaluation of bone marrow and neoplastic tissues plays a critical role in determining patient management and prognosis. Here, we highlight two cases in which the cytogenetic studies challenge the common practice of using hematologic and morphologic changes as key factors in malignant disease management. The first case is that of a lymph node sample from a 40-yr-old non-Hodgkin's lymphoma (NHL) patient sent for determination of disease progress. Hematologic studies showed no evidence of transformation to high-grade NHL (>15% blasts with rare mitotic figures). Cytogenetic studies of lymph node showed multiple clonal abnormalities, most notably a der(18) from a t(14;18) which is associated with high-grade NHL. After two cycles of chemotherapy with fludarabine, the patient did not show any clinical response, suggesting possible progression to high-grade lymphoma. The second case is of a patient with a history of human immunodeficiency virus and blastic natural killer leukemia/lymphoma. Hematologic studies of ascitic fluid classified the patient as having pleural effusion lymphoma whereas bone marrow analysis showed no malignancy. Bone marrow cytogenetic studies showed multiple clonal abnormalities including a t(8;14), which is commonly associated with Burkitt's lymphoma (BL). To our knowledge, this is the first case wherein a morphologically normal bone marrow showed presence of clonal abnormalities consistent with BL or Pleural effusion lymphoma. After two cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, the patient's general condition and ascitis improved and she was discharged. These studies clearly demonstrate that genetic changes often precede morphologic changes in a developing malignant condition. Therefore, the critical information needed for care of patients with malignant disorders may be incomplete or inaccurate if cytogenetic evaluation is overlooked.     

Lamivudine allows completion of chemotherapy in lymphoma patients with hepatitis B reactivation

Reactivation of hepatitis B virus in patients receiving chemotherapy for non-Hodgkin's lymphoma (NHL) may give rise to hepatitis, hepatic failure and death, and prevent further chemotherapy. We report four patients with NHL in whom hepatitis flare-up was observed after two (three patients) and six (one patient) cycles of chemotherapy. After spontaneous recovery, they were treated with Lamivudine (100 mg/day), which enabled completion of chemotherapy without further hepatitis B reactivation. In one patient, high-dose chemotherapy and autologous stem cell transplantation was also performed. These data suggest a possible role for Lamivudine in preventing hepatitis B reactivation during chemotherapy administration to chronic carriers of the hepatitis B virus. Moreover, it enabled the completion of both standard and high-dose chemotherapy in patients with previous hepatitis B reactivation.     

Gem-(R)CHOP versus (R)CHOP: a randomized phase II study of gemcitabine combined with (R)CHOP in untreated aggressive non-Hodgkin's lymphoma--EORTC lymphoma group protocol 20021 (EudraCT number 2004-004635-54)

Background: Despite recent improvements, many patients with aggressive non‐Hodgkin’s lymphoma (NHL) ultimately succumb to their disease. Therefore, improvements in front‐line chemotherapy of aggressive NHL are needed. Gemcitabine is active in lymphoma. Methods: We performed a randomized phase II trial of the addition of gemcitabine to standard CHOP chemotherapy with or without rituximab [(R)CHOP]. The trial was also designed to determine the maximal tolerated dose (MTD) of gemcitabine in this combination. Patients with previously untreated aggressive NHL were randomized to receive either eight cycles of (R)CHOP given every 3 wk or (R)CHOP combined with gemcitabine [Gem‐(R)CHOP]. Results: Twenty‐five patients were enrolled in the trial before early closure. Twelve were randomized to Gem‐(R)CHOP and 13 to (R)CHOP. MTD of gemcitabine was 800 mg/m² given on days 1 and 8; dose‐limiting toxicity was hematologic. Five patients (42%) treated with Gem‐(R)CHOP achieved complete response in comparison with 10 (77%) treated with (R)CHOP. Median time to treatment failure was 1.5 yr for Gem‐(R)CHOP and 3.1 yr for (R)CHOP. Three patients receiving Gem‐(R)CHOP had serious pulmonary toxicity, when compared to none receiving (R)CHOP. One patient died of pneumonitis. Conclusions: In this group of patients, addition of gemcitabine did not seem to improve outcomes. Gem‐(R)CHOP in previously untreated patients with aggressive NHL occasionally results in severe, potentially fatal, pulmonary toxicity.     

Excellent survival following two courses of COPAD chemotherapy in children and adolescents with resected localized B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study

High cure rates are possible in children with localized mature B-cell lymphoma (B NHL) using a variety of chemotherapeutic strategies. To reduce late sequelae, the duration and intensity of chemotherapy has been progressively reduced. The Lymphome Malins de Burkitt (LMB) 89 study reported long-term survival in almost all children with localized resected disease treated with two courses of COPAD (cyclophosphamide, vincristine, prednisolone and doxorubicin). This study was designed to confirm the effectiveness of this approach in a larger number of patients in a multinational co-operative study. The patient cohort was part of an international study (French-American-British LMB 96), which included all disease stages and involved three national groups. Patients in this part of the study had resected stage I or completely resected abdominal stage II disease. Following surgery, two courses of COPAD were given, without intrathecal (IT) chemotherapy. One hundred and thirty-two children were evaluable. Two of 264 (0.9%) courses were associated with grade IV toxicity (one stomatitis and one infection). With a median follow up of 50.5 months, the 4 year event-free survival is 98.3% and overall survival is 99.2%. Children with resected localized B-NHL can be cured with minimal toxicity following two courses of low intensity treatment without IT chemotherapy.     

Ifosfamide, etoposide, cytarabine, and dexamethasone as salvage treatment followed by high-dose cyclophosphamide, melphalan, and etoposide with autologous peripheral blood stem cell transplantation for relapsed or refractory lymphomas

High-dose chemotherapy (HD-CT) with autologous stem cell transplantation is considered to be the treatment of choice for relapsed high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) patients, but the optimal treatment has not yet been defined. We evaluated a salvage treatment regimen consisting of conventional cycles with ifosfamide, etoposide, cytarabine, and dexamethasone (IVAD) followed by two cycles of HD-CT consisting of cyclophosphamide, melphalan, and etoposide (CMV) with autologous stem cell support in patients with relapsed or refractory NHL (n = 59) and HL (n = 16). Response to IVAD was complete remission (CR) in 16 patients (21%), partial remission (PR) in 39 patients (52%), stable disease (SD) in 18 patients (24%), and progressive disease (PD) in two patients (2.7%). Of 70 patients treated with HD-CT, 41 patients (59%) showed a CR, 20 patients a PR (29%), eight patients a SD (11%), and one patient a PD (1.4%). The 5-yr overall survival for the entire group of patients was 29%, and for patients with NHL and HL 25%, and 38%, respectively. The respective event-free survival probabilities at 5 yr were 22%, 16%, and 31%. Seven treatment-related deaths due to septicemia (three), cardiac arrhythmia (one), pneumonia (one), pneumonitis (one), and toxic epidermal necrolysis (one) were observed. In multivariate analysis, an International Prognostic Index of > or = 2 and resistant disease to first-line chemotherapy were poor independent prognostic factors for the subgroup of patients with NHL. In conclusion, these results indicate that IVAD/CMV is feasible as a salvage therapy for lymphoma patients. This treatment is currently evaluated with the addition of rituximab.     

Long-term gonadal toxicity after therapy for Hodgkin's and non-Hodgkin's lymphoma

Summary With the increasing cure rate of patients treated for Hodgkin's and non-Hodgkin's lymphoma, the evaluation of late effects on gonadal function remains an important issue. The gonadal function of relapse-free long-term survivors with high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) were studied; 24 of 119 patients with NHL treated between 1980 and 1990 and 66 of 364 patients with HD treated between 1975 and 1990 at Hannover University Medical School, who were younger than 45 years of age and in complete remission at the time of evaluation for at least 24 months after completion of therapy, were included into the analysis. Of 24 patients with NHL, 1/10 women (10%) and only 3/14 men (21%) showed signs of gonadal dysfunction. Three of these four patients had been treated with combined modality therapy followed by maintenance COP chemotherapy, resulting in high cumulative doses of cyclophosphamide (range: 12–43 g). In comparison, 13/26 (50%) women with HD suffered from premature ovarian failure, and 26/40 (65%) men showed signs of gonadal dysfunction with significant FSH elevations. No significant difference in the incidence of gonadal toxicity existed in patients treated with combined modality who received irradiation to either supra- or infradiaphragmatic radiation fields in combination with chemotherapy (70% versus 62%). A comparison of the chemotherapy regimens used in patients with NHL or HD shows that patients from both groups had received comparable median cumulative doses of cyclophosphamide, vincristine, and adriamycin, but only patients with HD had additionally received a median cumulative dose of 13.3 g of procarbazine per patient. A tendency towards a higher incidence of gonadal toxicity with higher cumulative doses of procarbazine received was found in patients with HD. The frequency of gonadal dysfunctions is markedly lower in patients treated for non-Hodgkin's lymphoma than in patients treated for Hodgkin's disease, approximately half of whom will be affected by long-term gonadal toxicity. Although the use of more intensive radiotherapy in patients with HD compared with NHL patients makes the evaluation of the influence of radiotherapy on gonadal toxicity more difficult, the current retrospective analysis raises the concern that, in addition to infradiaphragmatic radiotherapy, the use of procarbazine in regimens for the treatment of HD, like COPP or MOPP, may be a possible explanation for the differences in gonadal toxicity observed between patients with HD and those with NHL. Regimens including procarbazine should be avoided in patients wanting to preserve fertility since alternative chemotherapies with at least equal efficacy are available.     

Combined chemotherapy including high-dose methotrexate in KSHV/HHV8-associated primary effusion lymphoma

Primary effusion lymphoma (PEL) is a rare KSHV/HHV8-associated high-grade non-Hodgkin's lymphoma (NHL) of B-cell origin, characterized by serous effusions in body cavities. Most patients are HIV-infected homosexual men with severe immunosuppression and other KSHV/HHV8-associated diseases such as Kaposi's sarcoma (KS). The prognosis is poor with a median survival of less than 6 months in most cohorts. The achievement of a sustained complete remission is rare. High-dose chemotherapy regimens are warranted to improve complete remission rate and survival. Seven patients with AIDS-associated PEL were treated with a combined chemotherapy including high-dose methotrexate followed by leucovorin rescue. In all cases, KSHV/HHV8 sequences were detected in the effusion samples using quantitative PCR assays. Five patients had a pre-existing KS, associated in three cases with multicentric Castleman's disease (MCD). Upon diagnosis, 6 patients received antiretroviral therapy, which was maintained during chemotherapy in 5 of them. At time of analysis, 3 out of 7 patients were in complete remission 18, 26, and 78 months after PEL diagnosis. Three patients died with a progressive PEL at 22, 67, and 153 days after diagnosis, and 1 patient died 9 months after PEL diagnosis with a MCD-associated plasmablastic NHL. Complete remission was obtained in 3 out of 7 patients treated for AIDS-associated PEL with combined chemotherapy containing high-dose methotrexate.     

Stage I high-grade non-Hodgkin's lymphomas: a retrospective analysis

BACKGROUND. The treatment strategy for stage I non-Hodgkin's lymphomas (NHL) is far from being clearly established. METHODS. Thirty-seven patients (pts) with clinical stage I high-grade NHL treated between 1983 and 1989 have been retrospectively reviewed. Nineteen pts were treated by radiotherapy (RT) alone; 14 pts received chemotherapy (CT) followed by adjuvant RT, 3 pts CT alone and 1 pt underwent surgery alone. All pts with bulky disease were submitted to combined therapy. RESULTS. Estimated 7-yr overall survival (OS) was 82%, while freedom from relapse (FFR) was 73%. No differences in OS and FFR were recorded with regard to the type of treatment, site of the tumor, sex or histology. CONCLUSIONS. Our conclusion is that stage I NHL, even with unfavourable histology, may be successfully treated with RT only; however, CT before RT may be recommended in pts with a higher risk of relapse, i.e. the presence of bulky mass.     

Checkpoint blockade treatment sensitises relapsed/refractory non-Hodgkin lymphoma to subsequent therapy

Patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) have limited options for salvage, and checkpoint blockade therapy (CBT) has little efficacy. Usage in solid malignancies suggests that CBT sensitises tumours to subsequent chemotherapy. We performed the first analysis of CBT on subsequent NHL treatment. Seventeen North American centres retrospectively queried records. The primary aim was to evaluate the overall response rate (ORR) to post-CBT treatment. Secondary aims included progression-free survival (PFS), duration of response (DOR) and overall survival (OS). Fifty-nine patients (68% aggressive NHL, 69% advanced disease) were included. Patients received a median of three therapies before CBT. Fifty-three (90%) discontinued CBT due to progression. Post-CBT regimens included chemotherapy (49%), targeted therapy (30%), clinical trial (17%), transplant conditioning (2%) and chimeric antigen receptor T cell (CAR-T) therapy (2%). The ORR to post-CBT treatment was 51%, with median PFS of 6·1 months. In patients with at least stable disease (SD) to post-CBT, the median DOR was significantly longer than to pre-CBT (310 vs. 79 days, P = 0·005) suggesting sensitisation. Nineteen patients were transplanted after post-CBT therapy. Median overall survival was not reached, nor affected by regimen. Prospective trials are warranted, as this may offer R/R NHL patients a novel therapeutic approach.     

High-dose therapy and autologous transplantation for lymphoma: The Peter MacCallum Cancer Institute experience

Abstract
Background: High-dose therapy (HDT) with autologous bone marrow or blood cell transplantation for the treatment of lymphoma commenced at Peter MacCallum Cancer Institute in 1986.
Aim: To examine the patient characteristics and outcomes of patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) treated with HDT and autologous transplantation at our Institute in the first 10 years of the service (1986–95).
Methods: A retrospective analysis was performed examining patient characteristics, prior chemotherapy regimens, pretransplant disease status, HDT regimen, source of stem cells, time for haematopoietic recovery, complications of transplantation, response rates, overall survival (OS) and progression-free survival (PFS).
Results: Sixty-seven patients with NHL were treated with an estimated 5-year OS rate of 44% (95% confidence interval (CI) 32–56%) and PFS rate of 34% (95% CI 21–44%). Factors independently predictive of an unfavourable PFS on multivariate analyses were presence of constitutional symptoms at transplant ( P < 0.002) and chemotherapy-resistant disease at transplant ( P = 0.02). Twenty-three patients with HD were treated with a 5-year predicted OS rate of 74% (95% CI 56–92%) and PFS rate of 57% (95% CI 36–77%). There was no difference in PFS for HD patients who relapsed either within 12 months of completion of front-line therapy or after this time ( P = 0.5). The transplant-related mortality for the entire cohort was 17%, with a progressive decrease over time.
Conclusion: HDT with autologous transplanta- tion achieves durable PFS and OS in patients with lymphoma. Improved patient selection, therapy modifications according to prognostic factors and ongoing improvements in supportive care should improve outcomes further. (Intern Med J 2001; 31: 279–289)     

Cost-minimization analysis of CHOP, fludarabine and rituximab for the treatment of relapsed indolent B-cell non-Hodgkin's lymphoma in the U.K.

The optimal therapy for patients with relapsed indolent B-cell non-Hodgkin's lymphoma is unclear. Combination chemotherapy such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) or purine analogues including fludarabine are frequently used and the anti-CD20 monoclonal antibody rituximab has recently been licensed for use. However, no comparative studies of these therapies have been reported. Since relapsed indolent B-cell NHL is generally regarded as incurable with current therapies, the place of each of these therapies is likely to be determined by their relative efficacy, toxicity and cost. We undertook a literature review and a retrospective analysis of patients receiving combination chemotherapy for relapsed indolent B-cell NHL at our institution to determine the response rates and the duration of response when treated with CHOP or fludarabine. Reported response rates and median response duration for these regimens are similar, and similar to those reported in phase II studies of rituximab. A cost minimization analysis was therefore conducted. The per patient costs for the treatment of drug-related adverse events were pound 5049 for CHOP, pound 2953 for fludarabine and pound 109 for rituximab. When costs of a full course of each treatment were compared, the costs per patient for CHOP, fludarabine and rituximab were pound 7210 (pound 5975-8445), pound 10022 (pound 8917-11126) and pound 6080 (pound 5892-6267) respectively. In this preliminary analysis, rituximab appeared to have a similar efficacy rate to CHOP and fludarabine, but had significantly fewer adverse events and a lower total cost per patient. These data require confirmation in a prospective randomized study with formal assessment of cost-effectiveness.     

Treatment with bortezomib in a patient with heavily pretreated refractory T-cell lymphoblastic lymphoma

T-cell lymphoblastic lymphomas are highly aggressive non-Hodgkin's lymphoma (NHL) and account for approximately 3% of all adult NHL histologies, with poor prognosis. We describe a 38-year-old patient with T-cell lymphoblastic lymphoma, who responds to bortezomib and doxorubincin combination, following a failure of conventional chemotherapy. Two months after treatment, the patient showed near complete remission of the lymphadenopathy. These data suggest a possible synergistic effect with bortezomib in combination with doxorubincin and dexamethasone. To our knowledge, this is the first case of T-cell lymphoblastic lymphoma treated with bortezomib.     

A population-based study of the outcome for patients with first relapse of Hodgkin's lymphoma

BACKGROUND: Our aims were to evaluate the response to salvage treatment in relation to initial treatment and to evaluate prognostic factors at the time of relapse in an unselected population of relapsing patients with Hodgkin's lymphoma (HL). PATIENTS AND METHODS: In total, 124 patients younger than 60 yr of age with initial diagnosis of HL in Sweden relapsed between 1985 and 1995. RESULTS: Fifty-eight patients relapsed after initial treatment with radiotherapy (RT) only, 62 after combination chemotherapy (CT), of whom 30 had received additional involved-field RT, and four after a short course of CT followed by extended-field RT. For 37 patients among the 58 relapsers after initial RT treated according to the recommendations of the National guidelines, the 5-yr Hodgkin-specific survival (HLS) was 85%, overall survival (OS) 73% and event-free survival (EFS) 62%, which is not inferior to survival in patients with primarily advanced stages. It was poorer in the 21 patients who initially had received RT only, even though they had been recommended for more extensive treatment. For patients initially treated with a full course (6-8 cycles) of CT the 5-yr HLS was 60%, OS 58% and EFS 22%. Bulky disease and age at diagnosis strongly affected survival in a multivariate analysis. CONCLUSIONS: Patients initially treated with RT who relapse have a favourable outcome, provided they have been treated according to the recommendations of the guidelines at the time of diagnosis. Initially bulky disease and, as a consequence, additional RT as part of the initial treatment negatively affect survival at relapse in patients initially treated with a full course of CT.     

利妥昔单抗联合化疗治疗B细胞非霍奇金淋巴瘤合并乙肝病毒感染的临床观察

目的探讨利妥昔单抗联合化疗（RCHOP方案）治疗非霍奇金淋巴瘤（NHL）合并乙型肝炎病毒（HBV）携带者的安全性和有效性。方法将2004年1月至2010年1月收治的32例B细胞NHL患者分为2组,A组（n=12）为感染HBV的患者,B组（n=20）为非感染HBV患者。A、B组均接受R—CHOP方案化疗4～6周期。A组化疗前应用拉米夫定抗病毒治疗1周。观察两组疗效、肝功能异常发生率。结果A组CR率为83．33％,B组CR率为85．00％（P〉0．05）。A组Ⅰ～Ⅱ级肝功能损害发生率为16．67％,B组15．00％（P〉0．05）,两组差异无统计学意义。两组患者中均未发生HBV再激活。结论感染HBV的NHL患者用R—CHOP方案治疗及在化疗前预防性、足疗程的抗病毒治疗,可降低HBV再激活风险,减少肝功能损害。     

Cost benefit and clinical efficacy of low-dose granulocyte colony-stimulating factor after standard chemotherapy in patients with non-Hodgkin's lymphoma

High costs of molecule-targeted drugs, such as rituximab, ibritumomab, and tositumomab have given rise to an economical issue for treating patients with non-Hodgkin's lymphoma (NHL). Granulocyte colony-stimulating factors (G-CSFs), which are also expensive, are widely used for treating neutropenia after chemotherapy. In Japan, lenograstim at 2 microg/kg (about 100 microg/body) or filgrastim at 50 microg/m(2) (about 75 microg/body) is commonly administered for patients with NHL after chemotherapy. Therefore, cost-effectiveness is an important issue in treatment for NHL. Patients with advanced-stage NHL who needed chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen with or without rituximab were enrolled in this randomized cross-over trial to investigate the efficacy and safety of low-dose G-CSF. Half of the patients were administered 75 microg filgrastim in the first course after neutropenia and 50 microg lenograstim in the second course, and the other half were crossed over. Forty-seven patients were enrolled in this cross-over trial, and 24 patients completed the trial. Frequencies and durations of grade 4 leukocytopenia and neutropenia were similar in the two groups. Severe infection was rare and was observed at similar frequency. Frequencies of antibiotics use were also similar. The total cost of G-CSF (cost/drug x duration of administration) was significantly lower in patients who received 50 microg lenograstim. Hence, a low dose of lenograstim might be safe, effective and pharmaco-economically beneficial in patients with advanced-stage NHL.     

Ifosphamide, etoposide and epirubicin is an effective combined salvage and peripheral blood stem cell mobilisation regimen for transplant-eligible patients with non-Hodgkin lymphoma and Hodgkin disease

A total of 143 patients with relapsed (n = 90), primary refractory (n = 32) and first line chemotherapy responsive (n = 21) non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD) were treated with IVE (ifosphamide, etoposide and epirubicin) chemotherapy with the intent to proceed to high-dose therapy with either autologous or allogeneic transplantation, following peripheral blood stem cell mobilisation. A major response (complete/partial response) to IVE was seen in 115 patients (80.4%) with 5-year overall survival (OS) and event free survival (EFS) of 53% and 43%, respectively. Subgroup analysis showed overall response rates of 93.1% for HD with a 5-year OS and EFS of 62% and 52% respectively, while NHL showed response rates of 78.0% with 5-year OS and EFS of 50% and 39% respectively. The median number of CD34 +ve cells mobilised following IVE was 7.86 x 10(6) (range 1.72-42.91 x 10(6)), with 60% mobilising >2 x 10(6)/kg in a single collection. Grade IV neutropenia was seen in 79.6% patients and 77/270 cycles required intravenous antibiotic treatment. We conclude that IVE has a high response rate across a range of refractory and relapsed lymphoma with acceptable toxicity and excellent PBSC mobilising characteristics.     

Ocular presentation of primary central nervous system lymphoma: diagnosis and treatment

Primary ocular lymphoma (POL), a lymphoma of the globe, is a restricted form of primary central nervous system lymphoma (PCNSL) that often progresses to the brain and meninges; frequently it is misdiagnosed until central nervous system (CNS) lymphoma develops. The optimal treatment has not yet been identified. We retrospectively reviewed the course and the treatment of POL in 31 patients. Seventeen patients were treated for isolated POL (group A) and 14 were treated only after CNS disease was diagnosed (group B). The treatment in both groups consisted of systemic chemotherapy, chemotherapy plus radiotherapy (RT) or RT alone. In group A, nine patients (53%) developed CNS progression and five (29%) had ocular recurrence. In group B, seven (50%) had CNS progression and three (21%) ocular relapse. To control for diagnostic lead time, median survival was calculated from initial ocular symptoms and was 60 months in group A and 35 months in group B (P < 0.05). Ocular lymphoma responds to a variety of therapies but treatment with chemotherapy and/or ocular radiotherapy (ORT) failed to prevent CNS progression. Patients whose ocular disease was identified and treated before CNS progression had a significantly improved survival.     

Adult T-cell leukemia following long-term remission from non-Hodgkin's lymphoma

A female patient who had been initially diagnosed with non-Hodgkin's lymphoma (NHL) and achieved complete clinical remission with combined chemotherapy, developed overt adult T-cell leukemia (ATL) after 9 yr of disease-free survival. This is the first case of the development of ATL following the complete remission of NHL. Secondary malignant neoplasms are not well-documented in patients previously diagnosed with Hodgkin's disease. Although there have been a few reports concerning the occurrence of secondary malignancy in patients with non-Hodgkin's lymphoma (NHL), there has never been a documented case of ATL following long-term survival from NHL. Here, we report a case of typical adult T-cell leukemia (ATL) which occurred after 9 yr disease-free survival from NHL.