Primitive neuroectodermal tumor of urinary bladder: A case report and literature review.

RATIONALE: Primitive neuroectodermal tumor (PNET) of the urinary bladder is a highly aggressive tumor with high local recurrence and distant metastasis rates in cases of incomplete excision. We report a case of a young female patient, in whom early laparoscopic radical cystectomy combined with standard lymph node dissection and a modified vincristine, doxorubicin hydrochloride, and cyclophosphamide (VAC) chemotherapy regimen was controversial. Because PNET of the urinary bladder is a rare malignancy, the standard treatment regimen has not yet been established. It is not clear whether surgery combined with postoperative chemotherapy for PNET patients may be superior to surgery alone on long term survival. PATIENT CONCERNS: The patient was a 45-year-old Chinese woman who complained of lower urinary tract symptoms, including urgency, frequency, and difficulty in urination, for 2 months. DIAGNOSES: PNET. INTERVENTIONS: The patient underwent laparoscopic radical cystectomy and standard lymph node dissection, combined with modified VAC chemotherapy regimens. OUTCOMES: After undergoing radical surgery in 2018, the patient completed 6 courses of adjuvant chemotherapy. Abdominal and thorax computed tomography scanning was performed 3, 6, 9, and 12 months after the surgery was completely free of tumor. The patient is still alive with no signs of recurrent disease 2 years after diagnosis. LESSONS: Radical surgery and standard lymphadenectomy combined with adjuvant chemotherapy may be essential to improve the prognosis of PNET of the urinary bladder.

Is there uniformity in definitions and treatment of gestational trophoblastic disease in Europe?

OBJECTIVES: Because gestational trophoblastic disease is rare, little evidence is available from randomized controlled trials on optimal treatment and follow-up. Treatment protocols vary within Europe, and even between different centers within countries. One of the goals of the European Organization for Treatment of Trophoblastic Diseases (EOTTD) is to harmonize treatment in Europe. To provide a basis for international standardization of definitions, treatment and follow-up protocols in gestational trophoblastic disease, we evaluated differences and similarities between protocols in EOTTD countries. METHODS: Members from each EOTTD country were asked to complete an online structured questionnaire comprising multiple-choice and multiple-answer questions. The following themes were discussed: incidence of gestational trophoblastic disease and gestational trophoblastic neoplasia, definitions, guidelines, classification system, treatment, recurrence, and follow-up. RESULTS: Forty-four respondents from 17 countries participated in this study. Guidelines were present in 80% of the countries and the FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) staging and risk classification was often used to estimate risks. Agreement about when to start chemotherapy for post-molar gestational trophoblastic neoplasia was present among 66% of the respondents. Preferred first-line treatments in low- and high-risk gestational trophoblastic neoplasia were methotrexate (81%) and EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) (93%), respectively. The definition of human chorionic gonadotropin normalization after hydatidiform mole evacuation was two consecutive normal values for nine countries. The FIGO definition of post-molar gestational trophoblastic neoplasia based on human chorionic gonadotropin plateau or rise was agreed on by 69% of respondents, and only 69% and 74% defined low-risk and high-risk disease, respectively, using FIGO criteria. There were major differences in definitions of recurrence, chemotherapy resistance and follow-up protocols among countries, despite EOTTD consensus statements. CONCLUSIONS: This questionnaire provides a good overview of current clinical practices in different countries. Based on the survey results, it is clear that there are several gestationaltrophoblastic disease-related topics that need urgent attention within the EOTTD community to create more uniformity and to aid the development of uniform guidelines in Europe.

Potency and stability of compounded formulations of chlorambucil, melphalan and cyclophosphamide.

BACKGROUND: Oral chemotherapy agents are frequently compounded in veterinary medicine however, the potency of some formulations have been shown to vary from that of Food and Drug Administration (FDA)-approved products. AIMS: The objective of this study was to evaluate the potency and stability of three compounded oral chemotherapeutics commonly prescribed to be administered over time. MATERIALS & METHODS: Compounded chlorambucil 1 mg, cyclophosphamide 5 mg and melphalan 1 mg were obtained and for potency tested upon receipt and 6 weeks later. RESULTS: Potency ranged from 71 to 104% for chlorambucil and 58 to 109% for melphalan; 1/4 and 2/4 samples were <90% of labelled strength at baseline and 6 weeks, respectively, for both drugs. Potency of cyclophosphamide ranged from 92 to 107% with all samples +/-10% of labelled strength at all time points. DISCUSSION/CONCLUSION: These results demonstrate variability of compounded chemotherapy products, and highlight the need to consider both potency and stability when prescribing orally compounded chemotherapy.

Split calibration curve: an approach to avoid repeat analysis of the samples exceeding ULOQ.

BACKGROUND: The current practice of using calibration curves with narrow concentration ranges during bioanalysis of new chemical entities has some limitations and is time consuming. In the present study we describe a split calibration curve approach, where sample dilution and repeat analysis can be avoided without compromising the quality and integrity of the data obtained. RESULTS: A split calibration curve approach is employed to determine the drug concentration in plasma samples with accuracy and precision over a wide dynamic range of approximately 0.6 to 15,000 ng/ml for dapsone and approximately 1 to 25,000 ng/ml for cyclophosphamide and glipizide. A wide dynamic range of concentrations for these three compounds was used in the current study to construct split calibration curves and was successfully validated for sample analysis in a single run. CONCLUSION: Using this method, repeat analysis of samples can be avoided. This is useful for the bioanalysis of toxicokinetic studies with wide dose ranges and studies where the sample volume is limited.

Simultaneous determination of cyclophosphamide and 4-hydroxycyclophosphamide in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry - application to Chinese systemic lupus erythematosus patients.

BACKGROUND: A pharmacogenomics study of cyclophosphamide in systemic lupus erythematosus patients is being conducted in our laboratory in which the plasma concentrations of cyclophosphamide and its active metabolite 4-hydroxycyclophosphamide should be assayed rapidly and sensitively. METHODS: A rapid, stable and sensitive liquid chromato-graphy/electrospray ionization tandem mass spectrometry method was developed to simultaneously determine cyclophosphamide and 4-hydroxycyclophosphamide in human plasma with ifosfomide as an internal standard. After a protein precipitation with cold acetonitrile and stabilization of 4-hydroxycyclophosphamide by ansyldrazine and extraction with ethyl acetate, separation was performed on a C18 3.5 µm 2.1 × 50 mm column with mobile phase of acetonitrile and water (50:50, v/v) with 0.1% formic acid at 200 µL/min. The chromatographic run time was 3 min. RESULTS: The linear calibration curves ranged from 5 to 5000 ng/mL for cyclophosphamide and 5-500 ng/mL for 4-hydroxycyclophosphamide. The recoveries of the liquid extraction were 54.5%-58.5% for cyclophosphamide and 103.5%-105.5% for 4-hydroxycyclophosphamide. The lower limit of quantification was 5 ng/mL for both analytes. The intra- and inter-day precision was <15% for quality control samples at 4000, 500, 50 ng/mL for cyclophosphamide and 4-hydroxycyclophosphamide at 400, 100, 20 ng/mL. The method was applied in this pharmacogenomics study in Chinese systemic lupus erythematosus patients treated with low-dose cyclophosphamide. CONCLUSIONS: The method was efficient with shorter running time and lower limit of quantification compared to previous reports and has been successfully applied in this pharmacogenomics study.

Will BEACOPP be the standard for high risk Hodgkin lymphoma patients in advanced stages?

Hodgkin Lymphoma (HL) has become one of the most curable cancers, even in adulthood, through continuous improvement of therapeutic options and their verification by large multicenter trials. Today more than 95% of patients with HL in early stages and in advanced stages 85-90% can be cured. Nevertheless, these good results are threatened by treatment associated toxicities such as infertility, cardiopulmonary toxicity and secondary malignancies. It is therefore the aim of future trial generations both to maintain the excellent treatment results and to minimize late effects. In 1964 for the first time deVita et al. described the MOPP polychempotherapy for patients with advanced HL which led to cure rates in more than 50%. Around ten years later Bonadonna et al. established the non cross resistant alternative regime to MOPP, ABVD which nowadays is accepted as "gold standard" for the treatment of advanced HL. MOPP and/or ABVD and furthermore the alternating MOPP/ABVD or the MOPP/ABV hybrid with and without the help of consolidative radiation resulted in around 70% long term survival rates, 30-40% of patients experienced tumor progression or relapses within 5 years. This led the German Hodgkin Study Group (GHSG) [Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med 2003; 348: 2386-95] to improve the efficacy of COPP/ABVD by time- and dose-intensification, omission of Velban and Dacarbazin and adding Etoposide resulting in the BEACOPP principle. From the initial pilot studies in 1992 three trial generations, HD9, HD12, HD15, have now established this principle as one of the most effective chemotherapy regimen in advanced HL. We certainly hope that it will not last another 20 years to establish the BEACOPP regimen as an attractive curative treatment option for at least the high risk cohorts of HL.

Evaluation of the in vitro and in vivo genotoxicity of magnolia bark extract.

Magnolia bark extract (MBE) is an extract of the dried stem, root, or branch bark of magnolia trees that has been used historically in traditional Chinese and Japanese medicines, and more recently as a component of dietary supplements and cosmetic products. To study the genotoxic potential of MBE, a bacterial reverse mutation assay and an in vivo micronucleus test were conducted. Compositional analysis of the test substance revealed that MBE contains 94% magnolol and 1.5% honokiol. MBE exerted no mutagenic activity in various bacterial strains of Salmonella typhimurium and in Escherichia coli WP2 uvrA, either in the absence or presence of metabolic activation at all doses tested. In the micronucleus test, various doses of MBE did not affect the proportions of immature to total erythrocytes, nor did it increase the number of micronuclei in the immature erythrocytes of Swiss albino mice. The results of these studies demonstrate that MBE is not genotoxic under the conditions of the in vitro bacterial reverse mutation assay and the in vivo micronucleus test, and support the safety of MBE for dietary consumption.

Improved therapeutic outcomes of DLBCL after introduction of rituximab in Korean patients.

The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been shown to improve the outcome in all age groups with newly diagnosed diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis to evaluate the impact of this combination therapy on DLBCL outcomes in Korea. From October 2001 to June 2004, newly diagnosed DLBCL patients in nine Korean institutes were included. All of these 81 patients were treated with three or more cycles of rituximab plus CHOP (R-CHOP) combination chemotherapy (R group), and followed for a minimum of 12 months. For comparison, a historical cohort of patients was used and analyzed for "Clinicopathologic characteristics of Korean non-Hodgkin's lymphomas (NHLs) based on Revised American Lymphoma (REAL) classification" in 1999. Among the 1,098 NHL patients, the data of 214 DLBCL patients, who were treated with CHOP chemotherapy in first-line, were analyzed (C group). We compared outcomes between the C group and the R group. A total of 295 patients were evaluated (C group, 214; R group, 81). The complete response (CR) rate was higher in R group (73 vs 91%, p=0.001). The 2-year event-free survival (EFS) rate was significantly higher in R group (78 vs 85%, p=0.0194). This survival benefit was maintained in high-risk patients according to the international prognostic index (IPI) (p=0.0039), regardless of age. However, there was no significant difference in low-risk patients. The addition of rituximab to CHOP combination chemotherapy for DLBCLs showed improved outcomes, particularly in high-risk group according to the IPI. Long-term follow-up results will be needed to confirm these results.

The combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is feasible and can be an option for relapsed/refractory multiple myeloma.

INTRODUCTION: Thalidomide has recently proven to be a useful drug for treatment of refractory and relapsed multiple myeloma patients, up to 35% of whom achieve remission. However, little is known about the potential additive or synergistic effect upon its association with other drugs with proven efficacy in MM. MATERIAL AND METHODS: The present pilot study was designed to evaluate the toxicity and response rate of the association of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) in 22 refractory or relapsed MM patients. The protocol scheduled the administration of thalidomide at escalating doses (200 to 800 mg/day), daily oral cyclophosphamide (CTX) (50 mg/day) and pulsed dexamethasone (40 mg/day, four days every three weeks). RESULTS: Adverse effects were moderate (grade or=2 were noted. Other side effects included grade 50% M-component reduction (two of them with a complete remission). Only two responders have already progressed, with a projected event free survival of 51% at 12 months. Seven patients have died due to disease progression (n=5), sudden death (n=1) and infection (n=1). CONCLUSION: This study shows that ThaCyDex is a feasible and promising therapeutic approach for patients with relapsed/refractory MM.

Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens.

Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.

Cemp, a mitoxantrone containing combination, in the treatment of intermediate and high grade non-hodgkin's lymphoma: an effective and non toxic therapeutic alternative for adult and elderly patients.

Here we report the results of a randomised multicenter phase III clinical trial which assesses the therapeutic efficacy and tolerability of a chemotherapy protocol CEMP (cyclophosphamide, etoposide, mitoxantrone and prednisone) in adult and elderly patients with advanced intermediate and high-grade NHL. Between October 1991 and October 1995, 139 patients, aged 55 to 79 years, with diffuse intermediate and high-grade lymphoma, were enrolled. A considerable percentage of patients had clinically aggressive disease: 32.4% had systemic symptoms, 79% had stage III or IV disease, 33.8% had bone marrow involvement, 46% had splenic involvement and 42.5% had increased values of serum lactate dehydrogenate. Complete remission was achieved in 70 of the 139 patients (51.9%) and PR in 12 (16.6%) with an overall response of 68.5%. The overall response survival rate at 6 years was 39%, whereas DFS rate was 48.7% and PFS rate was 28.5%. At four years 49% of the patients were still in CR. Dividing the patients in two groups, under and over 65 years of age, we obtained the same results as far as overall response is concerned. No toxic deaths occurred, neither cardiac, renal nor liver complications happened. CEMP regimen is an effective and safe protocol with good results in elderly people, well comparable to those achieved in younger ones.

Acquired haemophilia: experiences with a standardized approach.

Acquired haemophilia is a rare, life-threatening, acquired bleeding diathesis. No general consensus exists on the best therapeutic approach. We report on the standardized approach at our institution evaluated in ten patients with acquired haemophilia. Factor VIII inhibitors were found in all patients, activities ranging from 1 to 648 Bethesda units (BU). Eight of the ten patients presented with severe bleeding. Two patients died during the acute phase, one from intracranial bleeding and one due to Mycoplasma pneumonia. One patient with mild bleeding was treated with immunosuppression alone. Two patients with factor VIII inhibitor activities below 5 BU were started on factor VIII concentrate therapy. Therapy was successful in one and was changed to recombinant human activated factor VII infusion (rFVIIa) in the other, owing to insufficient factor VIII recovery. Six patients with factor VIII inhibitor activities above 5 BU were started on activated prothrombin complex concentrate (APCC) therapy. APCC treatment was successful initially in all six patients and was changed to rFVIIa infusion in one for rebleeding. One patient did not receive any specific therapy. Immunosuppression with prednisolone (2 mg kg(-1)) was begun in nine patients and was continued with cyclophosphamide (2 mg kg(-1)) in six. A complete remission of the acquired haemophilia was found in seven of the eight patients surviving the acute phase, one had a partial remission. All patients with acquired haemophilia could be managed effectively following our standardized approach. Routine administration of immunosuppression was associated with high inhibitor elimination rates.

Primary mediastinal large B-cell lymphoma with sclerosis: a clinical study of 89 patients treated with MACOP-B chemotherapy and radiation therapy.

BACKGROUND AND OBJECTIVES: Primary mediastinal large B-cell lymphoma (PMLBCL) with sclerosis has recently been recognized as a specific clinical and pathologic entity for which the best therapeutic approach seems to be a combination of chemotherapy and radiotherapy. DESIGN AND METHODS: Between 1989 and 1998, 89 previously untreated patients with PMLBCL with sclerosis were treated with a combination of a third-generation chemotherapy regimen (MACOP-B) and mediastinal radiation therapy. The response evaluations were examined after chemotherapy and at the end of radiotherapy. RESULTS: Twenty-three (26%) patients achieved a complete response (CR) and 59 (66%) obtained a partial response (PR) after the MACOP-B regimen. After radiation therapy, 55/59 (93%) of the patients in PR achieved CR. The CR rate at the end of the treatment was 88% (78/89). Only 7 (8%) patients were non-responders. Among the 78 patients who obtained a CR there were 7 (9%) relapses in a median follow-up of 5 months (all relapses occurred within 9 months); the other 71 patients are currently in continuous CR with a median follow-upof 45 months (range, 4-110 months). Projected overall survival was 86% at 9 years; the relapse-free survival curve of the 78 patients who achieved CR was 91% at 9 years. INTERPRETATION AND CONCLUSIONS: In patients with PMLBCL with sclerosis, combined modality treatment using the MACOP-B chemotherapy regimen and radiation therapy induces a good remission rate with the patients having a greater than 90% chance of surviving disease-free at 9 years. Radiotherapy often plays a pivotal role in obtaining CR status.

High-dose therapy and autologous bone marrow transplantation for follicular lymphoma in first complete or partial remission: results of a phase II clinical trial.

Advanced stage follicular small cleaved and mixed cell lymphoma is characterized by relapse from remission and survival ranging from 6 to 12 years. Because young patients have the greatest compromise in longevity, the efficacy and toxicity of high-dose radiochemotherapy and bone marrow transplantation after conventional chemotherapy was evaluated in a prospective phase II clinical trial. Thirty-seven patients in a minimal disease state after conventional chemotherapy received fractionated total body irradiation and high-dose etoposide and cyclophosphamide, followed by purged autologous bone marrow. A reference sample of 188 patients of similar age, stage, and histology managed at this institution before 1988 was identified for comparison of patient characteristics and outcomes. Compared with reference patients, transplant recipients had a higher tumor burden at diagnosis. With a median follow-up of 6.5 years, the estimated 10-year survival after transplantation was 86%. There was a single lymphoma death yielding a 10-year disease-specific survival of 97%. There were 2 early transplant-related deaths and 2 late acute leukemia deaths. Ten patients relapsed, one with microscopic disease only. High tumor burden at diagnosis and incomplete response to chemotherapy adversely influenced survival in the reference but not in the transplanted patients. The estimated risk of death of 14% and relapse of 30% at 10 years in our transplanted follicular lymphoma patients, the majority of whom had high tumor burdens, compares favorably with our observations in appropriately matched reference patients.

Low-dose fludarabine and cyclophosphamide in elderly patients with B-cell chronic lymphocytic leukemia refractory to conventional therapy.

BACKGROUND AND OBJECTIVES: In recent years fludarabine alone or in combination with other drugs has been reported to be effective in the treatment of B-cell chronic lymphocytic leukemia (B-CLL), both as first line and salvage therapy. Among the different combination regimens, the association of fludarabine and cyclophosphamide has shown a considerable therapeutic efficacy, although a relevant number of infectious complications have been described, particularly in elderly patients. The aim of this work was to evaluate the efficacy, the toxicity, and the incidence of infectious episodes of a regimen combining lower doses of fludarabine and cyclophosphamide in elderly patients with B-CLL refractory to conventional therapy. DESIGN AND METHODS: Twenty patients with progressive B-CLL with a median age of 75 years (4 in stage B and 16 in stage C) and refractory to conventional therapy were enrolled in this study. The combination regimen was as follows: fludarabine 15 mg/m2/day i.v. [max 25 mg] and cyclophosphamide 200 mg/m2/day i.v. for four days. RESULTS: All patients enrolled were evaluable for response. Three out of 20 (15%) patients achieved a complete remission (CR), 14/20 (70%) a partial response (PR) with an overall response rate (CR+PR) of 85%, according to National Cancer Institute-Working Group response criteria. Three patients were considered resistant. In four out of 20 patients (20%), a severe neutropenia (neutrophils < 0.5x10(9)/L) occurred and one of them developed an infectious complication which required treatment with systemic antibiotics and granulocyte colony- stimulating factor (G-CSF). Non-hematologic toxicity was negligible in all patients but one, who despite a adequate therapy with allopurinol and hydration, experienced a tumor lysis syndrome with transient but severe renal impairment. INTERPRETATION AND CONCLUSIONS: The association of low-dose fludarabine and cyclophosphamide appeared to be effective in this subset of B-CLL patients, reproducing a similar overall response rate obtained with other fludarabine-based combination therapies. In addition, in this group of elderly patients, toxic side effects were negligible and infectious complications remarkably low.

Lymphoproliferative disease of granular T lymphocytes presenting as aplastic anemia.

Lymphoproliferative disease of granular T lymphocyte (T-LDGL), also known as T-cell large granular lymphocyte leukemia, is a clonal disorder of cytotoxic T lymphocytes that is clinically manifested as chronic neutropenia and anemia. Association with autoimmune disorders is common. In 9 patients, T-LDGL is reported as presenting as aplastic anemia. The clinical characteristics were similar to acquired aplastic anemia. Morphologic evidence of increased granular lymphocytes in the peripheral blood and an excess of CD3(+)/CD8(+)/CD57(+) cells in the bone marrow were found in most cases. Cyclophosphamide was ineffective, but noncytotoxic immunosuppressive agents generally produced a good response. After a median follow-up of 49 months, 5 patients had died from the disease or related complications. Median survival was 40 months. Aplastic anemia can be a presenting manifestation of T-LDGL, and T-LDGL should be considered in the differential diagnosis of acquired aplastic anemia.

Lomustine and melphalan cannot be replaced by cyclophosphamide and etoposide without reducing efficacy in MOPPEBVCAD chemotherapy for advanced Hodgkin's disease.

BACKGROUND AND OBJECTIVES: To evaluate the feasibility, toxicity and preliminary results of a potentially less toxic variant of the MOPPEBVCAD chemotherapy regimen for advanced Hodgkin's disease: MOPPEBVCyED, in which cyclophosphamide and etoposide replace lomustine and melphalan, respectively, with the remaining components being unaltered. DESIGN AND METHODS: The study was multicenter, prospective and randomized, and enrolled 67 patients with newly diagnosed stage IIB, III, IV Hodgkin's disease (62 were expected on the grounds of statistical considerations). Radiotherapy was restricted to sites of bulky involvement or to areas that responded incompletely to chemotherapy. Median follow-up was 48 months. RESULTS: Comparing MOPPEBVCAD vs. MOPPEBVCyED, the results were as follows: complete remissions 35/35 vs. 30/32 (plus one partial remission and one disease progression); relapses 5 vs. 8; deaths 2 (one of myelodysplasia) vs. 2; delivered mean dose intensity (DI): lomustine 0.79+/-0.67 vs. cyclophosphamide 0.82+/-0.32; melphalan 0.80+/-0.13 vs. etoposide 0.86+/-0.18; average DI of the 7 drugs common to both regimens 0.73+/-0.10 vs. 0.83+/-0.11; all 9 drugs 0.75+/-0.13 vs. 0.84+/-0.09 (p=0.002); projected 5-year failure-free survival 0.79 vs 0.62; second cancers, two myelodysplasias vs. one carcinoma of the kidney. Toxicities were not statistically different except for heavier thrombocytopenia being recorded with MOPPEBVCAD. INTERPRETATION AND CONCLUSIONS: The higher cumulative and single drug DI recorded with MOPPEBVCyED may reflect better short-term tolerability, but it does not lead to better disease control. Its late toxicity may be expected to be lower in the future but at present it does not seem to be a sufficient reason to substitute MOPPEBVCyED for MOPPEBVCAD.