A Rare Case of Good Outcome of Hodgkin Lymphoma in a Patient with HIV on Antiretroviral Therapy (ART).

BACKGROUND Recent reports have shown an increased incidence of Hodgkin lymphoma (HL) in patients treated with antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection. This report is of a case of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) with a good outcome in a 58-year-old Nigerian HIV-positive man who was being treated with ART. CASE REPORT A 58-year-old HIV-positive man presented to a clinic for evaluation of a left axillary mass. He was diagnosed with HIV in 2005, which was well-controlled by ART. He reported intermittent swelling in the left axillary region for several years. Results of a physical examination were significant for mild tender left anterior axillary lymphadenopathy. He had a computed tomography (CT) scan of the chest and neck, which showed left axillary adenopathy, with the largest measuring 3.5×2.0 cm. A staging positron emission tomography-computed tomography (PET/CT) showed focal uptake in 2 left axillary lymph nodes with no other sites involved. He underwent excision of the left axillary lymph node. Histopathology was consistent with nodular lymphocyte-predominant-type Hodgkin's lymphoma (NLHPL). He underwent radiation therapy with a total dose of 3600 centigray (cGy) according to National Comprehensive Cancer Network (NCCN) guidelines. The 5-month follow-up PET/CT scan showed no evidence of malignancy. CONCLUSIONS We present a case of HIV-associated NLHPL that had an indolent course and a good treatment outcome. This case highlights the importance of regular physical examination in HIV patients while on treatment with ART and accurate diagnosis of the cause of lymphadenopathy to prevent extra-nodal spread in cases of lymphoma.

Multicenter analysis of geriatric fitness and real-world outcomes in older patients with classical Hodgkin lymphoma.

We performed a multicenter retrospective analysis across 10 US academic medical centers to evaluate treatment patterns and outcomes in patients age ≥60 years with classic Hodgkin lymphoma (cHL) from 2010-2018. Among 244 eligible patients, median age was 68, 63% had advanced stage (III/IV), 96% had Eastern Cooperative Oncology Group performance status (PS) 0-2, and 12% had documented loss of ≥1 activity of daily living (ADL). Medical comorbidities were assessed by the Cumulative Illness Rating Scale-Geriatric (CIRS-G), where n = 44 (18%) had total scores ≥10. Using multivariable Cox models, only ADL loss predicted shorter progression-free (PFS; hazard ratio [HR] 2.13, P = .007) and overall survival (OS; HR 2.52, P = .02). Most patients (n = 203, 83%) received conventional chemotherapy regimens, including doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; 56%), AVD (14%), and AVD with brentuximab vedotin (BV; 9%). Compared to alternative therapies, conventional regimens significantly improved PFS (HR 0.46, P = .0007) and OS (HR 0.31, P = .0003). Survival was similar following conventional chemotherapy in those ages 60-69 vs ≥70: PFS HR 0.88, P = .63; OS HR 0.73, P = .55. Early treatment discontinuation due to toxicity was more common with CIRS-G ≥10 (28% vs 12%, P = .016) or documented geriatric syndrome (28% vs 13%, P = .02). A competing risk analysis demonstrated improved disease-related survival with conventional therapy (HR 0.29, P = .02) and higher mortality from causes other than disease or treatment with high CIRS-G or geriatric syndromes. This study suggests conventional chemotherapy regimens remain a standard of care in fit older patients with cHL, and highlights the importance of geriatric assessments in defining fitness for cHL therapy going forward.

Impact of delays in definitive treatment on overall survival: a National Cancer Database study of patients with Hodgkin lymphoma.

The purpose of this large observational study was to examine outcomes in patients with Hodgkin lymphoma (HL) by timing to definitive chemotherapy (TTC) using standard and propensity score (PS)-adjusted Cox proportional hazards models. From 1998-2011, 56,457 patients with stage I-IV HL were studied, with a median follow-up of 6.0 years (median age=39). Median TTC was 26 days from diagnosis. The cohort of "early" (<60 days from diagnosis) TTC patients included 45,307 (80.3%) patients and "late" (≥60 days) TTC was 11,150 (19.7%). Patients were more likely to experience early TTC if they were of a younger age, at an advanced stage, with "B" symptoms, favorably insured, favorable socioeconomic status, and treated at comprehensive cancer center (all p<0.05). Ten-year overall survival for patients with early TTC was 73.2% vs. 70.0% for those with late TTC (HR=0.87; 95%CI, 0.83-0.92, p<0.0001). After PS-matching for co-variates, early TTC was not associated with overall survival (HR=0.96; 95%CI, 0.85-1.08, p=0.51). This represents the only study to evaluate overall survival by time to definitive treatment for HL.

Management and controversies of classical Hodgkin lymphoma in pregnancy.

The goal of managing classical Hodgkin lymphoma (cHL) in pregnancy is to obtain good long-term outcomes for both the mother and fetus. Given the excellent outcomes outside of pregnancy, the goal of treatment should remain curative. There remains a tension and debate regarding the timing of chemotherapy, the curative nature of such treatment and the timing of delivery. Moreover, the aim during pregnancy should be to minimize fetal toxicity and optimize perinatal outcomes. The management of cHL within pregnancy was covered within the excellent recent British Committee for Standards in Haematology guidelines, but with necessary brevity. By reviewing the literature over the last 30 years, herein we discuss the options for management during each trimester. Critical organogenesis occurs between 2 and 8 weeks post-conception; during which time the immature fetus is vulnerable to cytotoxic exposure. We discuss the evidence for using ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) and single agent vinblastine in the first trimester. cHL presenting in pregnancy raises complex and difficult ethical dilemmas that can cause anxiety for patients, families and physicians. Decision-making must be multi-disciplinary and holistic, taking into account the patient's wishes, psycho-social and religious beliefs and personal circumstances. Clear communication between the haemato-oncologist, medical obstetrician, nurse specialists, midwives and neonatologists is paramount to a successful outcome.

[Granulomatous mycosis fungoides: combination therapy with bexarotene and PUVA]. / Granulomatöse Mycosis fungoides : Kombinationstherapie mit Bexaroten und PUVA.

A 74-year-old male with granulomatous mycosis fungoides presented with multiple, red-brown macules and plaques up to 8 cm in diameter, just as in classical mycosis fungoides. Dermatohistopathologic findings showed extensive granulomatous infiltrates, in which clonality could be detected in various locations via T cell receptor rearrangement. Granulomatous mycosis fungoides is a very rare form of mycosis fungoides with histological resemblance to granulomatous slack skin. It shows a rather aggressive course and can be challenging to diagnose. In our case, combination treatment with bexarotene and bath PUVA, as recommended in guidelines, resulted in an impressive improvement of the skin lesions within ten weeks.

Brentuximab vedotin: first-line agent for advanced Hodgkin lymphoma.

Hodgkin lymphoma (HL) is characterized by malignant Reed-Sternberg cells which express CD30. Current National Comprehensive Cancer Network guidelines for patients with advanced HL (stage III/IV disease) recommend adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), or escalated bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) as first-line regimens. ABVD appears to be as effective, with fewer side effects, as escalated BEACOPP. Escalated BEACOPP leads to a greater progression-free survival but no difference in overall survival. Recent advancements in technology have enabled an exciting shift to molecular-targeted cancer therapy. Brentuximab vedotin, a CD30-directed antibody conjugate, specifically targets malignant HL cells. It is approved by the Food and Drug Administration for the treatment of systemic anaplastic large-cell lymphoma and refractory HL that has progressed after autologous stem cell transplant, or after two prior multiagent chemotherapy regimens among patients ineligible to receive a transplant.

Newly discovered quick, non-invasive screening method of bone marrow malignancies including various leukemias, Hodgkin's lymphoma, non-Hodgkin's lymphoma, & multiple myeloma by abnormality of small rectangular area within bone marrow organ representation areas of the face.

Diagnoses of bone marrow associated malignancies such as Acute & Chronic Lymphocytic Leukemia, Acute & Chronic Myelogenous (Myeloid) Leukemia, Hodgkin's Lymphoma & Non-Hodgkin's Lymphoma, and Multiple Myeloma are often missed without a blood test. However, in 2008, Omura Y reported several newly discovered organ representation areas that exist between the lower end of the eyebrows and upper end of the upper eyelid. This space was divided into 5 organ representation areas. The first space (more than 1/4 of entire space) near the side of the face (temple) is the bone marrow representation area (BMRA). Therefore, we examined the bone marrow representation areas non-invasively using the Bi-Digital O-Ring Test (BDORT). When the small rectangular shaped part of the BMRA is strong negative (-) with more than -2, often there is a malignancy associated with bone marrow. In this area, we found 1) Integrin alpha5beta1 & Oncogen C-fos Ab2 increased very significantly between 125-300 ng BDORT units; 2) very high Chrysotile Asbestos (0.11-0.14 mg); 3) markedly reduced Acetylcholine of less than 1 ng; 4) significantly reduced telomere of less than 1 yg (= 10(-24) g); and 5) Increased 8-OH-dG (often more than 5 ng). Once the abnormal small rectangular area is localized by BDORT, by detecting the specific microscope slide which produces EMF (electromagnetic field) resonance, one can diagnose these malignancies non-invasively in about 10 minutes. When a subject has any one of the above 7 types of bone marrow associated malignancies, the 5 aforementioned abnormal parameters can be detected. When Acetylcholine is markedly reduced to 0.25 ng or less, 8-OH-dG is 10 ng or higher, and Sirtuin 1 (one of the 7 mammalian longevity genes products) in both the Hippocampus and the body is 0.025 pg or less, most of the patients have a very poor prognosis. However, we found that increasing normal cell telomere & longevity gene product Sirtuin 1 can often improve both pathology & prognosis. All measurements are in BDORT units (the weight required to produce maximum EMF resonance).

Centralised multidisciplinary re-evaluation of diagnostic procedures in patients with newly diagnosed Hodgkin lymphoma.

BACKGROUND: Hodgkin Lymphoma (HL) is highly curable when treated accurately. The challenge is to cure patients with the minimal risk of long-term complications. For that, optimal initial diagnostics are required to determine the optimal treatment plan. We offer non-academic hospitals in our Regional Comprehensive Cancer Centre network a centralised review of all diagnostic procedures from patients with newly diagnosed HL. We report our experience on concordances and discrepancies between local findings and central review results. PATIENTS AND METHODS: A haematologist and radiation oncologist at the Hodgkin Radboud University Nijmegen Medical Centre outpatient clinic examined all patients with newly diagnosed HL between February 2006 and May 2010. In a multidisciplinary lymphoma conference, diagnostic information is reviewed and treatment advice formulated. Discordant findings in pathology, staging and therapy were recorded as 'minor', no therapeutic consequences or 'major', adapted therapy advice. RESULTS: Altogether, 125 patients were included. Pathology review showed 86% concordance, with 4% major discordance, mainly nodular lymphocyte predominant sub-type. Revision of initial staging was concordant in 77%; however 15% major discordance of which most were upstaged. This resulted in 19% treatment adaption. CONCLUSION: Our findings highlight the discrepancies in interpretation of diagnostic tests. We advocate centralised review process for all newly diagnosed patients with HL.

Serum selenium concentration at diagnosis and outcome in patients with haematological malignancies.

We have previously reported presentation serum selenium level to be predictive of outcome in diffuse large B-cell lymphoma. This has now been studied in a further 430 patients, 163 with acute myeloid leukaemia (AML), 156 with Hodgkin Lymphoma (HL), and 111 with Follicular Lymphoma (FL). Serum selenium was below the UK normal reference range in 45% of patients, and correlated with serum albumin (r=0·24-0·46, P<0·001-0·003) in all tumour types. Independent predictors of presentation selenium were; French-American-British subtype and albumin (P<0·001 for both) in AML, haemoglobin (P=0·002) and B-symptoms (P=0·01) in HL, and albumin (P<0·001) in FL. In AML and HL, response to first line therapy was lower in patients with low serum selenium, but selenium was no longer predictive of response when other variables were entered into a multivariate model. Low selenium was also associated with a worse overall survival in FL [Hazard Ratio (HR) 2·3, 95% confidence interval (CI) 1·4, 4·0] and a trend to a worse overall survival in AML (HR 1·43, 95% CI 0·96, 2·13) by univariate Cox regression analysis, but not by multivariate analysis. In conclusion, low serum selenium is associated with a worse outcome in patients with haematological malignancies, but is not independently predictive, suggesting that it reflects other factors.

A pilot study of addition of amifostine to melphalan, carboplatin, etoposide, and cyclophosphamide with autologous hematopoietic stem cell transplantation in pediatric solid tumors-A pediatric blood and marrow transplant consortium study.

Limited information is available regarding the use of amifostine in pediatric hematopoietic stem cell transplant (HSCT) patients. Melphalan, carboplatin, etoposide +/- cyclophosphamide is a commonly used preparatory regimen in pediatric solid tumor HSCT. Therefore, we decided to determine the feasibility of the addition of amifostine (750 mg/m b.i.d. x 4 d) to melphalan (200 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) (level 1) and escalating doses of cyclophosphamide (3000 mg/m and 3800 mg/m, levels 2 and 3, respectively) followed by autologous HSCT. Thirty-two patients with a variety of pediatric solid tumors were studied. Seventeen patients were accrued at level 1, 9 at level 2, and 6 at level 3. Major toxicities during the administration of the preparatory regimen were hypocalcemia, emesis, and hypotension. Hypocalcemia required aggressive calcium supplementation during the conditioning phase. No dose limiting toxicities were encountered at level 3. Amifostine at 750 mg/m b.i.d. for 4 days can be administered with a double alkylator regimen consisting of melphalan (200 mg/m), cyclophosphamide (up to 3800 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) with manageable toxicities.

Malignancies in beta-thalassemia patients: a single-center experience and a concise review of the literature.

Thalassemia represents the world's most common monogenic disease, characterized by absence of or decreased globin chain production. The lifespan of thalassemia patients has been extended as a result of current supportive treatment. We report three cases of cancer (non-Hodgkin lymphoma, Hodgkin disease, and seminoma) in thalassemic patients. Factors that may contribute to the pathogenesis of cancer seem to be infections and iron overload through mechanisms of oxidative damage; immunomodulation or coexistence of the two diseases may only be coincidental.

Hair selenium status in children with leukemia and lymphoma.

Selenium (Se) is a trace element contributing to the structure of antioxidant system that saves cells from reactive oxygen species. Low serum Se levels have been reported in pediatric and adult patients with cancers. On the other hand, hair Se levels, predicting the long-term body Se status, have been reported in only adult patients with cancer. The aim of the study was to investigate the hair Se status in children with newly diagnosed lymphoid malignancies and the relation between malnutrition and Se deficiency. Thirty patients with leukemia (n=17) and lymphoma (n=13), and 25 healthy controls were enrolled to the study. Se was determined with atomic absorption spectrophotometrical method. Hair Se levels of the patients were significantly lower than those of control group [666.96+/-341.46 ng/g vs. 1019.22+/-371.83 ng/g (P<0.001)]. Children with lymphoma had lower Se than the children with acute lymphoblastic leukemia but not statistically significant [547.03+/-283.67 ng/g vs. 758.67+/-361.05 ng/g (P>0.05)]. Malnourished patients (11/30) had lower hair Se levels (483.51+/-235.55 ng/g) than those of the controls (P=0.036), whereas the Se levels of the patients who had no malnutrition (773.17+/-352.92 ng/g) were also lower than those of the controls but not statistically significant (P=0.053). There was no correlation between age, sex, and the hair Se levels. In this study, we found that hair Se levels of the children with leukemia and lymphoma, especially those of malnourished patients, were lower than those of controls. Additional studies are needed to determinate whether low levels of hair Se may play a role in carcinogenesis.

Infarto talámico bilateral y cognición en paciente con enfermedad de Hodgkin / Bilateral thalamic infarction and cognition in patient with Hodgkin's disease

La afectación del sistema nervioso central en la enfermedad de Hodgkin (HDG) es excepcional. Los pacientes con lesiones malignas tienen mayor riesgo de infarto cerebral. Se presentó un paciente con antecedente de enfermedad de HDG quien presentó episodios súbitos de deterioro del nivel de conciencia y que en el período de recuperación mostró severas alteraciones en sus funciones psíquicas superiores con trastornos groseros de la memoria de fijación y evocación, desorientación témporo-espacial, acalculia, perseveraciones, conducta inadecuada y agresividad. Se determinó, mediante estudios imagenológicos, tomografía axial computarizada y resonancia magnética nuclear, el diagnóstico de infarto talámico bilateral. Se concluyó que las lesiones del tálamo que se acompañan de alteraciones de las funciones psíquicas superiores de carácter demencial son comúnmente bilaterales y que es importante diagnosticar estas complicaciones porque la mayoría son tratables. Se recomendó realizar estudios neuropsicológicos periódicos para precisar si existe recuperación evolutiva de los trastornos cognitivos y conductuales o concluir su diagnóstico como una demencia vascular talámica(AU)

Factores pronósticos en los linfomas: linfomas no Hodgkin y linfoma deHodgkin / Prognostic factors in lymphomas: non-Hodgkin's lymphomas and Hodgkin's lymphoma

La patología tumoral linfoide, que incluye tanto los linfomas no hodgkinianos como el linfoma de Hodgkin, representa un grupo muy heterogéneo de neoplasias que tienen en común su origen en la proliferación de células linfoides detenidas en diferentes etapas de su desarrollo madurativo. Así pues, se incluyen dentro de los linfomas enfermedades muy distintas desde el punto de vista histológico, clínico y evolutivo, que precisan de tratamientos que dependen en gran medida de la agresividad del linfoma y deben ajustarse al riesgo que presenta cada enfermo en concreto. Para valorar dicho riesgo resulta imprescindible conocer el pronóstico aproximado de los pacientes, en función de una serie de variables iniciales y evolutivas que se relacionan con el tipo de respuesta al tratamiento y la supervivencia: son los factores pronósticos. (AU)

Abnormal flow volume loops in patients with intrathoracic Hodgkin's disease.

STUDY OBJECTIVES: To study the incidence of upper airway obstruction, as measured on the flow volume loop (FVL), in patients with bulky mediastinal Hodgkin's disease; to correlate the FVL with CT of the chest; and to follow the changes in the FVL after treatment of the tumor. DESIGN: Retrospective study of pulmonary function tests (PFTs) and chest CTs performed as part of a clinical trial for Hodgkin's disease. SETTING: Memorial Sloan-Kettering Cancer Center, a comprehensive cancer care center. PATIENTS: Twenty-five patients (15 men and 10 women; age range, 20 to 57 years) with bulky mediastinal Hodgkin's disease enrolled in a clinical trial of chemotherapy followed by external beam radiation therapy. MEASUREMENTS AND RESULTS: Fourteen of 25 patients (56%) had an abnormal FVL prior to therapy; after chemotherapy, only 7 of 25 patients (28%) had an abnormal FVL. The abnormal patterns seen were either those typical of fixed obstruction or variable extrathoracic obstruction. No patient had a pattern typical of variable intrathoracic obstruction. On chest CT scan, 16 patients had grade-I tracheal deformity; 6 had grade-II deformity, and 3 had grade-III deformity. All three patients with grade-III deformity had a fixed obstruction pattern, as did three patients with a grade-I pattern. Patients with a fixed pattern on FVL had significant decreases in inspiratory and expiratory flow rates. CONCLUSION: FVL abnormalities suggesting upper airway obstruction occurred in > 50% of patients with bulky mediastinal Hodgkin's disease. A fixed pattern of obstruction was associated with the lower flow rates and severe tracheal distortion on CT; these patients may warrant special attention prior to general anesthesia or invasive procedures. Asymptomatic patients with abnormal FVLs but normal tracheal profiles need not undergo extensive evaluation. No patients showed the expected pattern typical of intrathoracic obstruction, but rather the major effect was on the inspiratory loop. The authors speculate on the mechanism for this unexpected finding.

Primer caso de enfermedad de hodgkin primitiva del colon en Arequipa

La enfermedad de Hodgkin primitiva del colon, sólo se ha reportado un caso en Arequipa, diagnosticado y tratado en el Hospital Regional Honorio Delgado de Arequipa. Se trata de una paciente de sexo femenino, de 53 años de edad, que ingresa con un tiempo de enfermedad de cuatro meses, presentando alza térmica, sudoración nocturna, baja de peso, dolor abdominal y diarreas líquidas. Al examen se encuentra tumorización en fosa iliaca derecha de 15x10 cms. Se le indica estudios radiográficos (enema baritado de colon) y ecografía abdominal, donde se concluye como un cáncer de colon; fué operada realizándosele una hemicolectomia derecha, ileotransversoanastomosis términoterminal y colecistectomia. El informe anatomopatológico concluye como tumor de Hodgkin de Celularidad Mixta, catalogada como un estadío IIIB. Es dada de alta y reingresa después de cuatro meses, en mal estado general, presentando una recidiva de la enfermedad. Se le realizan exámenes auxiliares (hematométricos, bioquímica sanguínea, radiográficos, tomográficos y biopsias (hueso y médula ósea)). Encontrándose una enfermedad activa, de mal pronóstico, con la existencia de adenomegalias retroperitoneales e infiltración de intestino, mesenterio, pleura, hígado y hueso. Recibe tratamiento con radioterapia (3000 rad.) y quimioterapia (MOPP), lo que origina una leucopenia y neutropenia severas, que asociado a un síndrome anémico, síndrome pleuroparenquimal bilateral, hipoproteinemia y insuficiencia renal, la conducen a una sepsis y muerte posterior de la paciente. No se le realiza autopsia por negativa de familiares.

75Se-Selenite scrintigraphy in the clinical staging of malignant lymphomas.

The value of 75Se-selenite scintigraphy in clinical staging was investigated in 45 patients with Hodgkin's disease and in 28 patients with non-Hodgkin's lymphoma. Of these, 9 patients had recurrence of previously treated lymphomas. The scintigraphic results were compared with clinical, cytologic, histologic and radiographic findings in different anatomic regions. 75Se-selenite scintigraphy resulted in 6 to 20 per cent false negative findings, 15 to 43 per cent false positive and 12 to 20 per cent equivocal evaluations, the accuracy being least in the abdominal region. The relatively high rediation dose delivered by 75Se-selenite, furthermore, makes it less attractive for use in the primary diagnosis of malignant lymphomas.