Hodgkin's Disease Patients Research Articles

Increased risk for invasive aspergillosis in patients with lymphoproliferative diseases after autologous hematopoietic SCT

The risk of invasive aspergillosis (IA) is considered to be low among autologous HSCT recipients, but an increase in the incidence has been observed recently in this setting. The aim of the study was to assess the influence of immunosuppressive drugs (steroids, rituximab, fludarabine, thalidomide), used in treatment of lymphoid malignancies during 6 months of pretransplant period, on IA incidence after autologous HSCT. A total of 109 patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD) and multiple myeloma (MM), conditioned with carmustine, etoposide, cytarabine, melphalan or melphalan and transplanted with PBSC, were analyzed prospectively. Patients were monitored with twice-weekly galactomannan test. High-resolution computed tomograhy of the chest and bronchoscopy were performed in case of positive galactomanan test, persistent fever or pulmonary infiltrates. Documented IA was diagnosed in nine (8%) patients (three proven, six probable). The incidence of IA was comparable in NHL, HD and MM patients and not influenced by age, advanced disease or conditioning regimen. Factors significant for development of documented IA by univariate analysis were treatment with fludarabine (P=0.008) or rituximab (P=0.039). The only factor predicting documented IA by multivariate analysis was treatment with fludarabine (P=0.008). Patients treated with fludarabine or rituximab in pretransplant period are at risk of IA and require close monitoring and/or anti-mould prophylaxis.

The use of the MammoSite balloon applicator in re-irradiation of the breast

Purpose To examine the feasibility of using the MammoSite brachytherapy applicator in the retreatment of the previously irradiated breast. Methods and materials Between March 2004 and March 2007, three patients previously treated with external beam radiotherapy were retreated using the MammoSite brachytherapy device. Two patients were treated for an ipsilateral breast tumor recurrence after breast conservation surgery and postoperative irradiation, whereas the third patient developed an in-field breast cancer likely associated with Hodgkin's disease mantle irradiation 27 years before. The recurrent histology of two was ductal carcinoma in situ ([DCIS] one originally presenting as infiltrating ductal carcinoma [IDC] and the other as DCIS), whereas the Hodgkin's disease patient presented with IDC. All patients received a twice-daily tumor dose of 3400 cGy at 340 cGy/fraction. The mean maximum skin dose was 53.4% (range, 49.5–60.3%) of the prescribed dose. Results With a mean followup of 32 months, no patient developed a local recurrence. Cosmesis in all three cases as graded by the National Surgical Adjuvant Breast and Bowel Project, cosmesis criteria was excellent (Grade I) in all cases. Dosimetric calculations demonstrated that the device allows for appropriate local irradiation while sparing the previously irradiated skin of the involved breast as defined by the protocol standard. Conclusions Use of the MammoSite device in the treatment of the previously irradiated breast is feasible and may provide adequate local control as well as acceptable cosmesis in carefully selected patients.

The valencia programme for fertility preservation

Fertility preservation needs have increased dramatically in recent years due to a rising cancer incidence and also a significant increase in survival rates. We report on 200 women participating in the Valencia Programme for Fertility Preservation, of whom 55% were breast cancer patients, 25% Hodgkin's disease patients, and the remaining 20% suffered from other nonmalignant and malignant diseases. Mean age was 28.2 years (11-39). Before patients were submitted to oncological treatment, the right ovarian cortex was extracted by laparoscopy and cryopreserved. Once the patient was free of disease, the right ovarian cortex was thawed and implanted onto the left ovarian medulla (after extraction at the same surgical time of left ovarian cortex). In 95% of cases, a piece approximately 2 x 3 cm was obtained. The procedure did not cause any change in the cancer therapy schedule. Four implants had been performed (all of them in women who underwent chemotherapy prior to ovarian cortex extraction), from which two of the case achieved ovarian function resumption, in one case a month after the implant and in the other 5.5 months after. The remaining two implanted cases were performed 5 and 6 months prior to the writing of this paper, respectively. Ovarian tissue cryopreservation is a feasible option to preserve ovarian function and possibly fertility in adolescents and young women at risk of developing premature ovarian failure (POF) due to chemotherapy and/or radiotherapy.

Bone marrow and peripheral blood natural killer cell activity in lymphomas. Its response to IL-2.

Natural killer (NK) cytotoxic activity was simultaneously investigated in bone marrow mononuclear cells (BMMC) and peripheral blood lymphocytes (PBL) from nine Hodgkin's disease (HD) and 15 non-Hodgkin lymphoma (NHL) untreated patients. Twenty-five PBL samples and seven bone marrow specimens from healthy individuals were also included as control group (C). NK cell activity was evaluated in basal condition and post-stimulation with human recombinant IL-2 (rIL-2). Data were expressed in K values (number of BMMC or PBL needed to lyse 50% of the target cells). In basal condition, both HD and NHL patients showed a NK cell activity comparable to the C group, both in BMMC (HD, K = 2.48 +/- 1.3; NHL, K = 3.8 +/- 2.0; C, K = 3.2 +/- 0.7) and PBL (HD, K = 2.0 +/- 1.0; NHL, K = 2.3 +/- 1.0; C, K = 2.2 +/- 0.2). Stimulation with rIL-2 induced a significant and comparable enhancement of the NK activity in PBL from HD, NHL and C while the response to rIL-2 of the BMMC in most of the HD and NHL patients was significantly greater than the C group. Responder cells were characterized by negative selection with specific MoAb plus complement as a CD3-, CD16+, CD56+ cytotoxic cell and further confirmed by flow cytometry. We postulate that IL-2 activation of bone marrow NK cell precursors, in addition to enhancing the activity of circulating NK, may be of value for the therapeutic rationale of IL-2 in patients with lymphoma.

Secondary malignant neoplasms among children and adolescents following treatment for Hodgkin disease

10055 Background: While 90% of patients diagnosed with Hodgkin disease (HD) during childhood are successfully treated, these patients remain at risk for late effects from these therapies. The objective of the current study was to evaluate the frequency of and risk factors for secondary malignant neoplasms (SMNs) among a cohort of HD patients who were treated at Roswell Park Cancer Institute (RPCI) between 1960 and 1989. Methods: This was a retrospective cohort study of 182 previously untreated patients with HD who were younger than 20 years of age at the time of diagnosis and were referred to RPCI between 1/1/1960 and 12/31/1989; follow-up extended through 12/31/2007. Sex- and age-specific person-years at risk were accumulated and applied to gender, age-, and time period-specific cancer incidence rates for New York State, excluding New York City. Standardized incidence ratios (SIRs), and 95% confidence intervals, were calculated for overall cancer incidence and by type of therapy. Results: Of 182 individu...

F18 fluorodeoxyglucose uptake in progressive transformation of germinal centres

FDG-PET/CT is a widely established imaging modality for staging, restaging and monitoring therapy response in lymphoma patients. Progressive transformation of germinal centres (PTGC) is a benign condition presenting characteristically as asymptomatic lymphadenopathy. This paper presents a case of a 53-year-old man with a history of Hodgkin’s disease (HD) whose F18 FDG-PET/CT scan showed high uptake in left axillary lymph nodes (SUV 3.8). A subsequent, left axillary lymph node biopsy revealed PTGC. PTGC can present as a false positive finding on FDG-PET/CT in lymphoma patients and biopsy should be done in HD patients in clinical remission but have a positive FDG-PET/CT scan.

Autologous Cytokine-Induced Killer Cells as Post-Transplant Cellular Immunotherapy.

Disease relapse remains a major cause of treatment failure following autologous hematopoietic cell transplantation (HCT) for patients with high-risk malignancies. Cellular immunotherapy using activated autologous effector cells to recognize and kill tumor targets in a minimal disease state after transplant is a novel strategy to reduce relapse and improve survival. In this phase I/II study, we investigated the safety and efficacy of administering ex-vivo expanded autologous cytokine-induced killer (CIK) cells as post-transplant cellular immunotherapy. Patients with high risk recurrent or refractory Hodgkin's disease (HD)- defined as B symptoms at relapse, pulmonary or bone marrow disease at relapse and more than minimal disease at the time of transplantation- and patients with multiple myeloma (MM) and acute myelogenous leukemia undergoing single autologous HCT were eligible. The autologous CIK cells were ex-vivo expanded from an aliquot of the patient's autologous apheresis product for 21–28 days in the presence of IFN-γ, IL-2, and OKT-3 to a maximal cell dose of 2×108 CIK cells/kg. The CIK cell population is uniquely characterized by having the functional and phenotypic properties of both T cells and NK cells, (i.e. expressing CD3 and CD56 molecules) and kills tumor targets through an NKG2D-mediated mechanism. A single infusion of CIK cells was given on day 42–63 following autologous transplantation. Monitoring for infusion-related toxicities was performed for the first 28 days. Disease response assessments were done at day 90, 180, one year and annually. Correlative studies on cytokine profile, primary tumor cytotoxicity and NKG2D ligand expression are being performed. Thirteen patients (ages 19–64) have received autologous CIK cell infusions to date. Nine patients have high risk HD; four patients have MM with a single autologous HCT. The median CIK cell dose for infusion was 0.9×108 cells/kg (range 0.2–2×108/kg). The only infusional toxicities observed have been one grade 1 headache and one grade 1 nausea- both were transient and resolved. Hematologic parameters have not been affected by the infusion. In vitro cytotoxicity of cultured CIK cells was assessed against a panel of leukemia and lymphoma cell lines including Jurkat, DB, OCI-Ly8 and SUDHL4. Median 51-Cr release at 40:1 (E:T) ranged from 71% killing against Jurkat cells to 21% against DB. The first patient on the trial with high risk HD involving the lung and bone marrow is one year from HCT without evidence of disease relapse. Four other patients (all high risk HD) have completed day 180 disease response assessments and have no evidence of disease relapse. One HD patient had progressive disease at day 100. The three evaluable MM patients have no disease progression at day 90–180. In this first phase of study, we have confirmed the safety of administering autologous CIK cells at a single maximal dose at day 42–63 post-transplant. Maintenance of disease response in these high risk patients is encouraging in the first year following transplantation.

The Role of Bone Marrow Examination in the Initial Evaluation of Pediatric Hodgkin' Disease: The Canadian Perspective.

Hodgkin's Disease (HD) is the most common lymphoma affecting young adults and teenagers. Bone marrow involvement is rare but if present, infers Stage IV disease and an inferior outcome. Adult studies have suggested that bone marrow examination (BME) may not be necessary unless certain risk factors are present. However, some pediatric centers continue to perform BME routinely on all children with HD. BME is invasive and generally performed under conscious sedation in children. We validated and administered an internet-based survey to examine the practice of all Canadian pediatric oncologists regarding BME in children with HD. We also retrospectively evaluated the impact of routine BME on the HD patients treated at our institution over the past 27 years. Forty-three percent of eligible physicians (n=93) completed the survey and 16 of a total of 17 Canadian pediatric oncology centers were represented. BME universally consisted of bilateral bone marrow aspirates and trephine biopsies. Routine BME for Stage III and IV disease was consistently practised nationally (by 92% and 97% of respondents, respectively). By contrast, 54% and 70% of respondents reported performing routine BME in low stage (Stage I and II) disease, respectively. Respondents were more likely to report performing routine BME in low stage patients, if their pediatric hematology/oncology training was entirely outside Canada (p=0.04 for Stage I and p=0.07 for Stage II) and if they practiced at smaller centers (p=0.05 for Stage I and p=0.03 for Stage II). There were no differences in practice regarding BME associated with the number of years in practice or the number of patients seen annually by the respondent. If not part of routine staging for all patients, BME was more likely performed if there were “B” symptoms, cytopenias, and/or bulky disease. Most respondents (95%) would proceed with BME following a positive PET scan. In the review of local institutional practice, 62 patients with HD and BME were eligible for analysis. Only 4 patients (6.5%) had a positive BME. No patient with otherwise low stage disease was found to have bone marrow involvement. Two patients, who would have been assigned as Stage III disease, were upstaged to Stage IV due to their BME. Comparison of staging with and without BME demonstrated no significant difference. Hemoglobin level was found to be the to be the only significant risk factor for marrow involvement based on univariate analysis(put in statisticp=0.006). Age, gender, histologic subtype, presence of “B” symptoms, and other blood parameters (white count, platelets, ESR and transaminases) were not significant factors. Practice regarding BME in children with low stage HD is highly variable across Canada. Bone marrow examination in pediatric patients with low stage HD should be abandoned, unless there is a specific indication to do so (for example positive PET scan or unexplained anemia). Moreover, BME does not appear to add any additional therapeutic direction for higher stage patients.

High Dose Sequential (HDS) Followed by Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Salvage Treatment of Hodgkin's Disease (HD): A Brazilian Experience.

From May 1998 to November 2006, 77 HD patients who used the regimen of high dose cyclophosphamide HD (CY) 7 or 4g/m2, methotretaxe 8g/m2 and etoposide 2g/m2 followed by AHSCT were analyzed. Their median age was 25.8 (8.8–71.5) years, 46 males and 31 females. At diagnosis 50 (65%) were stage III or IV disease, 10 (13%) had bone marrow involvement, 29 (37.7%) bulky disease and 55 (71.4%) B symptoms. Besides that, all patients were submitted to a mean of 2 (1–4) chemotherapy lives and their status were 3 (3.9%) complete remission (CR), 17 (22.1%) partial remission (PR), 57 (74%) progression disease (PD) or in non-specified sensitivity relapse. Concerning CY dose 30 (39%) received 4 g/m2 and 47 (61%) received 7 g/m2. After the HDCY 16 (20.8%) were in CR, 22 (28.6%) PR, 28 (36.3%) remained in DP and 11 (14.3%) died most in PD. After a median follow-up of 3.97 (1.13–55.9) months, 53 (68.8%) patients were submitted to AHSCT and their present status is 30 alive [18 CR, 2PR and 10 DP]; 23 dead [2 CR, 14PD and 7 related to the procedure]. Overall survival for transplanted patients was 55% in 8 years. Currently we have 33/77 (43%) alive patients, 19 CR, 3 PR, 11 PD. Overall Survival (OS) for whole group was 32%, Disease Free Survival (DFS) 64% and Progression Free Survival (PFS) 40%. Patients who were in DP or relapse prior to the HDCY (57) compared to their status after that had a significant improvement (P=0,001), their OS was 40% to CR-PR group (24) versus 16% PD group (33). In general, mortality was 44 (57%), their cause was 19 PD (43.2%), 8 (18.2%) related to HDCY, 2 (4.5%) related to HDMTX, 7 (16%) related to AHSCT, 6 (13.6%) infections, 1 (2.3%) chronic GVHD after a reduced intensity conditioning regimen transplant and 1 (2.2%) AML. Besides that, 3 patients developed MDS and 1 developed AML. In conclusion, although it had happened a significant number of toxicity related deaths, the sequence is feasible, mainly for sensitive patients and presents an acceptable response. The authors emphasize the high frequency of poor prognosis patients and occurrence of MDS/AML in 4 (5.2%) patients.

Non-Myeloablative Allogeneic Transplantation for Hodgkin's and Non-Hodgkin's Lymphoma: Evidence for a Graft-Versus-Lymphoma Effect and Relevance of Chimerism.

The role of non-myeloablative allogeneic stem cell transplantation (NST) in the treatment of patients with Hodgkin’s disease (HD) or non-Hodgkin’s lymphoma (NHL) is still undefined. We report the outcomes of 87 patients with lymphoma who underwent NST at our institution. Thirty-six patients had HD and 51 had NHL (13 indolent NHL (indNHL), 23 aggressive NHL (aggNHL), and 15 mantle cell lymphoma (MCL)). Median age was 46 (18–64). Patients had received a median of 4 prior lines of therapy; 94% of the HD patients had received a previous autograft, as had 49% of NHL patients. 28% of patients were transplanted in CR, 49% in PR, and 23% with stable or progressive disease. The conditioning regimen consisted of IV busulfan (0.8 mg/kg/d × 4) and fludarabine (30 mg/m2/d × 4). Donors were matched related (38%), matched unrelated (56%), or mismatched (6%). Most patients received GVHD prophylaxis with a calcineurin inhibitor plus sirolimus or methotrexate. All patients engrafted. The 3-year cumulative incidence of non-relapse mortality (NRM) was 23%, and of relapse was 50%. The cumulative incidence of grade 2–4 acute GVHD was 16%, and the 2-year incidence of chronic GVHD was 68%. With a median follow-up of 21 months for survivors, the projected 3-year overall survival (OS) was 59% for patients with HD, 79% for indNHL, 42% for aggNHL, and 36% for MCL. The corresponding figures for 3-year progression-free survival (PFS) were 17% for HD, 59% for indNHL, 21% for aggNHL, and 30% for MCL. Figure Figure Multivariate analysis identified elevated pre-transplantation LDH and more than 4 prior lines of therapy as adverse factors for PFS, while indolent NHL histology was a favorable factor. In time-dependent multivariable models, grade 3–4 acute GVHD was associated with increased NRM and relapse, and decreased PFS and OS. Chronic GVHD was associated with a lower risk of relapse and improved PFS, without a significant effect on OS. The protective effect of chronic GVHD on relapse applied to all histologies except for aggNHL. Forty-five percent of relapsed patients (13 pts with HD and 5 with aggNHL) received donor lymphocyte infusion (DLI). The overall response rate (ORR) was 15% (2/13) for patients with HD, with both patients remaining progression-free at last follow-up; ORR was 40% (2/5) for patients with aggNHL, but responses were transient. For all patients, median chimerism at day 20–50 was 97% (range 46–100). Low early donor chimerism was not predictive of relapse, PFS, or OS in univariate or multivariate analyses. Moreover, relapse was not associated with loss of chimerism. Finally, chimerism at the time of DLI had no apparent bearing on its outcome. Conclusions: NST results in high PFS for indolent NHL. There is evidence of a graft-versus-lymphoma effect. Chimerism is not at any point predictive of relapse or of outcome. Future research could be aimed at increasing specific anti-lymphoma immune activity to harness GVL without increasing the incidence of GVHD.

AMD3100 plus G-CSF can successfully mobilize CD34+ cells from non-Hodgkin's lymphoma, Hodgkin's disease and multiple myeloma patients previously failing mobilization with chemotherapy and/or cytokine treatment: compassionate use data

AMD3100 given with G-CSF has been shown to mobilize CD34+ cells in non-Hodgkin's lymphoma (NHL), multiple myeloma (MM), and Hodgkin's disease (HD) patients who could not collect sufficient cells for autologous transplant following other mobilization regimens. These poor mobilizers are usually excluded from company-sponsored trials, but have been included in an AMD3100 Single Patient Use protocol, referred to as a Compassionate Use Protocol (CUP). A cohort of 115 data-audited poor mobilizers in CUP was assessed, with the objective being to collect > or =2 x 10(6) CD34+ cells per kg following AMD3100 plus G-CSF mobilization. The rates of successful CD34+ cell collection were similar for patients who previously failed chemotherapy mobilization or cytokine-only mobilization: NHL -- 60.3%, MM -- 71.4% and HD -- 76.5%. Following transplant, median times to neutrophil and PLT engraftment were 11 days and 18 days, respectively. Engraftment was durable. There were no drug-related serious adverse events. Of the adverse events considered related to AMD3100, two (1.6%) were severe (one patient -- headache, one patient -- nightmares). Other AMD3100-related adverse events were mild (84.8%) or moderate (13.6%). The most common AMD3100-related adverse events were gastrointestinal reactions, injection site reactions and paresthesias. AMD3100 plus G-CSF offers a new treatment to collect CD34+ cells for autologous transplant from poor mobilizers, with a high success rate.

Soluble CD30 serum level--an adequate marker for allograft rejection of solid organs?

The CD30 molecule, a 120 kDa cell surface glycoprotein, is a member of the tumor necrosis factor receptor (TNF-R) superfamily and was originally identified on the surface of Reed-Sternberg cells and anaplastic large cell lymphomas in Hodgkin's disease patients. In addition to lymphoproliferative disorders the expression of CD30 was found in both activated CD8+ and CD4+ Th2 cells which lead to the activation of B-cells and consequently to the inhibition of the Th1-type cellular immunity. The membrane-bound CD30 molecule can be proteolytically cleaved, thereby generating a soluble form (sCD30) of about 85 kDa. Low serum levels of soluble CD30 were found in healthy humans, whereas increased sCD30 serum concentrations were detected under pathophysiological situations such as systemic lupus erythematosus, rheumatoid arthritis, certain viral infections and adult T cell leukaemia/lymphoma. In addition, it has recently been suggested that pre- or post-transplant levels of sCD30 represent a biomarker for graft rejection associated with an impaired outcome for transplanted patients. We here review (i) the current knowledge of the clinical significance of sCD30 serum levels for solid organ transplantations and (ii) our own novel data regarding inter- and intra-individual variations as well as time-dependent alterations of sCD30 levels in patients. (iii) Based on this information the implementation of sCD30 as predictive pre-transplant or post-transplant parameter for solid organ transplantation is critically discussed.

Lymphomas of the head and neck in the pediatric population

Little is known about the incidence and survival outcomes of pediatric patients with head and neck (HN) lymphomas in Asian populations. This study sought to identify the incidence of HN involvement of pediatric lymphomas and to identify factors prognostic of patient survival. We reviewed the medical records of all children aged 0-14 years with previously untreated lymphomas of HN region and compared patient clinicopathologic characteristics and final outcomes in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Potential prognostic factors for patient survival were investigated. Of 106 eligible lymphoma patients, 45 (42.5%; 31 boys and 14 girls) showed HN involvement. Overall, NHL (n=37) showed more unusual and aggressive presentations than did HD (n=8) in the head and neck region. Cervical lymphadenopathy was frequently observed (30/45, 66.7%) in these patients. Involvement of extralymphatic head and neck sites was found in 15 of 37 NHL patients (40.5%) but not in any HD patients (p=0.027). Five-year disease-free survival (DFS) of all HN lymphoma patients was 76.0%. On multivariate analysis, advanced stage and absence of complete remission following 3 cycles of chemotherapy were poor prognostic indicators of patient survival (p<0.05). The incidence of HN involvement in pediatric lymphomas was 42.5% in the studied population. Stage of the lesion and early response to chemotherapy were independent factors prognostic of patient survival.

TTV infection in colorectal cancer tissues and normal mucosa

Department of Medicine II, Medical Faculty Mannheim, University of Heidelberg and the Molecular Gastroenterology Unit,Deutsches Krebsforschungszentrum, Heidelberg, GermanyDear Sir,Genetic modifications and environmental factors are presentlyseen as the key factors in the etiology of colorectal cancer,

Evolución, mediante estudios con 18F-FDG, de un caso de enfermedad de Hodgkin tipo esclerosis nodular después de tratamiento y autotrasplante

Positron Emission Tomography (PET) has become a very useful tool for monitoring Hodgkin's disease patients in the last years. When there is suspicion of disease persistence after treatment, this technique makes it possible to evaluate treatment activity of the residual lesions observed in the CT scan. Furthermore, due to the whole body study, new tumor sites, which very often change the therapeutic option, can be detected. We must take into account, however, that 18F-FDG is a very sensitive but not very specific tumor marker, since some inflammatory or infectious conditions may be associated to significant radiopharmaceutical uptakes. Thus, in order to increase specificity it is mandatory to correlate the PET information with the rest of the conventional imaging and clinical data and evolution of the patient. We present the case of a woman with Hodgkin's disease in which 18F-FDG PET was included in the follow-up. Both conditions, tumor and infection, were present in different times of the course. The integration of all the x-ray, clinical, laboratory and metabolic information allowed for a better and correct management of this patient.

Cost-effective therapy remission assessment in lymphoma patients using 2-[fluorine-18]fluoro-2-deoxy-D-glucose–positron emission tomography/computed tomography: is an end of treatment exam necessary in all patients?

The aim of this study was to evaluate the necessity of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) after end of treatment in lymphoma patients who had an interim FDG-PET/CT. In 38 patients with Hodgkin's disease (HD) and 30 patients with non-Hodgkin's lymphoma (NHL) interim PET/CT (intPET) after two to four cycles of chemotherapy and PET/CT after completion of first-line treatment (endPET) were carried out. Cost reduction was retrospectively calculated for the potentially superfluous endPET examinations. In 31 (82%) HD patients, intPET demonstrated complete remission (CR) which was still present on endPET. The remaining seven HD patients (18%) had partial remission (PR) on intPET. For NHL, 22 (73%) patients had CR on intPET analysis which was still present on endPET. In the remaining eight NHL patients, intPET revealed PR in seven and stable disease in one patient. None of all intPET complete responders progressed until the end of therapy. Thus, of the 196 PET/CT's carried out in our study population, 53 endPET's (27.0%) were carried out in interim complete responders. End-treatment PET/CT is unnecessary if intPET shows CR and the clinical course is uncomplicated. An imaging cost reduction of 27% in our study population could have been achieved by omitting end of treatment FDG-PET/CT in interim complete responders.

Myocardial Infarction Mortality Risk After Treatment for Hodgkin Disease: A Collaborative British Cohort Study

Myocardial infarction is a major cause of excess long-term mortality in survivors of Hodgkin disease, but limited information exists on the effects of specific chemotherapy regimens used to treat these patients on their risk of death from myocardial infarction. We followed a cohort of 7033 Hodgkin disease patients who were treated in Britain from November 1, 1967, through September 30, 2000, and compared their risk of myocardial infarction mortality with that in the general population of England and Wales. All statistical tests were two-sided. A total of 166 deaths from myocardial infarction occurred in the cohort, statistically significantly more than expected (standardized mortality ratio [SMR] = 2.5, 95% confidence interval [CI] = 2.1 to 2.9), with an absolute excess risk of 125.8 per 100,000 person-years. Standardized mortality ratios decreased sharply with older age at first treatment, but absolute excess risks of death from myocardial infarction increased with older age up to age 65 years at first treatment. The statistically significantly increased risk of myocardial infarction mortality persisted through to 25 years after first treatment. Risks were increased statistically significantly and independently for patients who had been treated with supradiaphragmatic radiotherapy, anthracyclines, or vincristine. Risk was particularly high for patients treated with the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (SMR = 9.5, 95% CI = 3.5 to 20.6). Risk at 20 or more years after first treatment was particularly great for patients who had received supradiaphragmatic radiotherapy and vincristine without anthracyclines (SMR = 14.8, 95% CI = 4.8 to 34.5). The risk of death from myocardial infarction after treatment for Hodgkin disease remains high for at least 25 years. The increased risks are related to supradiaphragmatic radiotherapy but may also be related to anthracycline and vincristine treatment.

Comparison of positron emission tomography and lymphangiography in the diagnosis of infradiaphragmatic hodgkin's disease

To evaluate the respective roles of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) and lymphangiography (LAG) in staging Hodgkin's disease (HD) patients with negative contrast-enhanced infradiaphragmatic computed tomography (CT). 28 patients underwent FDG-PET and LAG at initial staging. Concordant positive findings on both tests were regarded as actual HD locations and concordant negative findings as true negative. In case of discrepancy, the reference was biopsy or magnetic resonance imaging (MRI). Concordant results were obtained in 26 patients (24 negative, two positive). In two of the 24 negative patients, PET showed additional lesions in the spleen and one celiac lymph node (one patient), and in the right kidney and the right iliac crest (one patient). Discordant results were obtained in two patients. Both methods indicated infradiaphragmatic involvement in different locations in one patient. In the other, PET was falsely positive (PET done within 24 hours after a negative LAG), which was confirmed by biopsy (benign inflammatory, probably due to LAG medium). FDG-PET and LAG gave comparable results, making invasive LAG unnecessary. Furthermore, LAG, when performed before PET, can be responsible for false-positive PET results.

Reduced‐intensity allogeneic transplantation in patients with refractory or progressive Hodgkin's disease after high‐dose chemotherapy and autologous stem cell infusion

We analysed the feasibility and efficacy of allogeneic stem cell transplantation (allo-SCT) with reduced-intensity conditioning (RIC) in patients with refractory or progressive Hodgkin's disease (HD) after high-dose chemotherapy (HDCT). Fourteen patients with HD received allo-SCT with RIC: eleven patients had a human leucocytes antigen-identical related donor and three a matched unrelated donor. Six had chemoresistant disease and eight had chemosensitive one at the time of transplantation. All patients received a fludarabine-based RIC. All patients engrafted and full donor chimerism was achieved in all patients. Grade II acute graft-vs.-host disease (GvHD) developed in six of the 14 patients (43%). Chronic GvHD developed in eight of the 13 patients (61%). There was neither early nor late treatment-related mortality (TRM). With a median follow-up of 21 months (range 3-74), 10 of the 14 patients were alive (71%). Estimated overall survival at 1 and 2 yr was 93% and 73%, respectively, for the whole population, 83% and 44% respectively for patients with chemoresistant disease and 100% for those with chemosensitive disease. Estimated progression-free survival at 1 yr was 36%; 62.5% for chemosensitive patients and 0% for those with chemoresistant disease. In conclusion, allo-SCT with fludarabine-based RIC is a feasible procedure, without TRM in HD patients relapsed and refractory after HDCT. Even if several questions are still open, this approach should proposed for these poor prognosis patients.

Treatment Outcomes and Toxicities of ABVD Combination Chemotherapy Compared with CVPP in Hodgkin's Disease

Background: We retrospectively evaluated the treatment outcomes and toxicities of Hodgkin's disease (HD) patients treated by ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) combination chemotherapy, and compared them with those of a historical group treated with a CVPP (cyclophosphamide, vinblastine, procarbazine, and prednisone) regimen. Methods: The medical records of patients who had been diagnosed with HD histologically and treated by either ABVD or CVPP from 1997 to 2006 at the Korea University Medical Center were retrospectively reviewed. Results: Thirty patients were eligible. Nineteen patients received ABVD and eleven patients were treated with CVPP. The response rates for ABVD and CVPP were 84.21% and 54.55%, respectively. Median overall survival was 43.17 months for ABVD and 43.27 months for CVPP (P=.570). Median event-free survival was 39.03 months for ABVD and 16.73 months for CVPP (P=.088). There was no significant difference in median survival or in event-free survival between the two regimens. Hematologic toxicities were significantly more common in the CVPP group than in the ABVD group. Grade 3 or 4 neutropenia was observed in 72.72% of the CVPP group and in 36.84% of the ABVD group (P=.050). Conclusion: ABVD for HD showed significantly lower hematologic toxicities and moderately better treatment outcomes than did CVPP.