Chemotherapy plus radiation treatment is effective in controlling
stage IA or IIA nonbulky Hodgkin’s lymphoma in 90% of patients but is
associated with late treatment-related deaths. Chemotherapy alone may
improve survival because it is associated with fewer late deaths.
We randomly assigned 405 patients with previously untreated stage IA
or IIA non-bulky Hodgkin’s lymphoma to treatment with doxorubicin,
bleomycin, vinblastine, and dacarbazine (ABVD) alone or to treatment with
subtotal nodal radiation therapy, with or without ABVD therapy. Patients in
the ABVD-only group, both those with a favorable risk profile and those with
an unfavorable risk profile, received four to six cycles of ABVD. Among
those assigned to subtotal nodal radiation therapy, patients who had a
favorable risk profile received subtotal nodal radiation therapy alone and
patients with an unfavorable risk profile received two cycles of ABVD plus
subtotal nodal radiation therapy. The primary end point was 12-year overall
The median length of follow-up was 11.3 years. At 12 years, the rate
of overall survival was 94% among those receiving ABVD alone, as compared
with 87% among those receiving subtotal nodal radiation therapy (hazard
ratio for death with ABVD alone, 0.50; 95% confidence interval [CI], 0.25 to
0.99; P = 0.04); the rates of freedom from disease progression were 87% and
92% in the two groups, respectively (hazard ratio for disease progression,
1.91; 95% CI, 0.99 to 3.69; P = 0.05); and the rates of event-free survival
were 85% and 80%, respectively (hazard ratio for event, 0.88; 95% CI, 0.54
to 1.43; P = 0.60). Among the patients randomly assigned to ABVD alone, 6
patients died from Hodgkin’s lymphoma or an early treatment
complication and 6 died from another cause; among those receiving radiation
therapy, 4 deaths were related to Hodgkin’s lymphoma or early toxic
effects from the treatment and 20 were related to another cause.
Among patients with Hodgkin’s lymphoma, ABVD therapy alone, as
compared with treatment that included subtotal nodal radiation therapy, was
associated with a higher rate of overall survival owing to a lower rate of
death from other causes. (Funded by the Canadian Cancer Society and the
National Cancer Institute; HD.6 ClinicalTrials.gov number, NCT00002561.)
To assess therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) risk in patients treated for Hodgkin lymphoma (HL) on successive generations of Stanford clinical trials.
Patients and Methods
Patients with HL treated at Stanford with at least 5 years of follow-up after completing therapy were identified from our database. Records were reviewed for outcome and development of t-AML/MDS.
Seven hundred fifty-four patients treated from 1974 to 2003 were identified. Therapy varied across studies. Radiotherapy evolved from extended fields (S and C studies) to involved fields (G studies). Primary chemotherapy was mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or procarbazine, mechlorethamine, and vinblastine (PAVe) in S studies; MOPP, PAVe, vinblastine, bleomycin, and methotrexate (VBM), or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in C studies; and VbM (reduced dose of bleomycin compared with VBM) or mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) in G studies. Cumulative exposure to alkylating agent (AA) was notably lower in the G studies compared with the S and C studies, with a 75% to 83% lower dose of nitrogen mustard in addition to omission of procarbazine and melphalan. Twenty-four (3.2%) of 754 patients developed t-AML/MDS, 15 after primary chemotherapy and nine after salvage chemotherapy for relapsed HL. The incidence of t-AML/MDS was significantly lower in the G studies (0.3%) compared with the S (5.7%) or C (5.2%) studies (P < .001). Additionally, in the G studies, no t-AML/MDS was noted after primary therapy, and the only patient who developed t-AML/MDS did so after second-line therapy.
Our data demonstrate the relationship between the cumulative AA dose and t-AML/MDS. Limiting the dose of AA and decreased need for secondary treatments have significantly reduced the incidence of t-AML/MDS, which was extremely rare in the G studies (Stanford V era).
Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm arising from the antigen-presenting cells of the immune system. This disease usually involves the lymph nodes, and rarely, extranodal sites may be affected. The authors report a case of extranodal IDCS presenting in the pleura. A 32-yr-old man presented with progressive chest pain. Imaging studies showed diffuse pleural thickening with pleural effusion. Morphological and immunohistochemical analysis of an incisional biopsy of the pleura were consistent with a diagnosis of IDCS; tumor cells were positive for S100 and CD45, but negative for CD1a, CD21, CD35, B cell and T cell markers. The patient was administered chemotherapy, but died of progressive disease. Although its incidence is extremely rare, this case suggests that extranodal IDCS should be considered in the differential diagnosis of undifferentiated neoplasms and that immunohistochemical staining be performed using appropriate markers.
Dendritic Cell Sarcoma; Interdigitating; Pleura
There is a lack of contemporary prospective data examining the ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and Stanford V (SV; doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, prednisone) regimens in older Hodgkin lymphoma (HL) patients. Forty-four advanced-stage, older HL patients (aged ≥60 years) were treated on the randomized study, E2496. Toxicities were mostly similar between chemotherapy regimens, although 24% of older patients developed bleomycin lung toxicity (BLT), which occurred mainly with ABVD (91%). Further, the BLT-related mortality rate was 18%. The overall treatment-related mortality for older HL patients was 9% versus 0.3% for patients aged <60 years (p<0.001). Among older patients, there were no survival differences between ABVD and SV. According to age, outcomes were significantly inferior for older versus younger patients (5-year failure-free survival: 48% vs 74%, respectively, p=0.002; 5-year overall survival: 58% and 90%, respectively, p<0.0001), while time-to-progression (TTP) was not significantly different (5-year TTP: 68% versus 78%, respectively, p=0.37). Furthermore, considering progression and death without progression as competing risks, the risk of progression was not different between older and younger HL patients (5 years: 30% and 23%, respectively, p=0.30); however, the incidence of death without progression was significantly increased for older HL patients (22% versus 9%, respectively, p<0.0001). Thus, the marked HL age-dependent survival differences appeared attributable primarily to non-HL events.
Hodgkin lymphoma; elderly; treatment-related toxicity; bleomycin lung toxicity
In HIV patients, haemophagocytic syndrome (HPS) may occur in the presence of cancer, concomitant viral infection, HIV primo-infection or at the initiation of highly active antiretroviral therapy (HAART). Hodgkin lymphoma remains a rare cause of HPS. We describe a case of HPS with very high Epstein Barr virus (EBV) load in a HIV patient as initial manifestation of Hodgkin lymphoma.
Materials and Methods
A 29-year-old HIV positive man, successfully treated with HAART with an undetectable viral load and CD4 cells count of 438/µl, was admitted for high fever of unknown origin. Laboratory results showed a pancytopenia with haemoglobin at 82 g/l, lymphocyte count at 0.36G/l and platelets count at 47G/l; a highly elevated ferritine >7500 µg/l; increased lactate dehydrogenase at 885U/l and soluble IL2 receptor (CD25) >60 ng/ml. EBV load was measured and confirmed at 2,600,000 copies/ml. A PET-CT imaging showed diffuse elevated metabolic activity in the bone marrow and in two lesions in the spleen without lymphadenopathy. Bone marrow and liver biopsies revealed images of haemophagocytosis and lymphocyte depleted Hodgkin lymphoma. Treatment consisted in etoposid, steroids, and R-ABVD (rituximab, doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy. The patient completed six cycles of chemotherapy. We reviewed the literature in PubMed with the following keywords: HPS, HIV, EBV, Hodgkin lymphoma.
We identified four publications and two reviews reporting cases of HPS associated with Hodgkin lymphoma in HIV patients with either a positive EBV load either the presence of encoded EBV RNA in tumour cells. Twenty-two cases (including one pediatric case) were described. Among adults, mostly men, the median age was <50 years and immune suppression was marked with a median CD4 cell count<100 cells/µl, even in patients receiving HAART. When measured, EBV load in the serum was high. Prognosis was poor with a high mortality despite adequate treatment consisting in steroids and chemotherapy, with or without etoposide (Table 1).
Our case report and the review of literature suggest that physicians should be aware of the association between EBV infection/reactivation and Hodgkin lymphoma as a cause of HPS in HIV patients, even if successfully treated with HAART. The pathogenesis of these three interrelated conditions (viral infection, oncogenesis and immunologic reaction) remains unclear.
The metastatic propensity of invasive ductal carcinoma (IDC) of the breast correlates with axillary node involvement and with expression of the proliferation antigen Ki-67, whereas ductal carcinoma in situ (DCIS) is non-metastasising. To clarify whether concomitant DCIS affects IDC prognosis, we compared Ki-67 expression and node status of size-matched IDC subgroups either with DCIS (IDC-DCIS) or without DCIS (pure IDC).
We analysed data from 1355 breast cancer patients. End points were defined by the association of IDC (with or without DCIS) with grade, nodal status, Ki-67, and ER/HER2.
Size-matched IDC-DCIS was more likely than pure IDC to be screen detected (P=0.03), to occur in pre-menopausal women (P=0.002), and to be either ER-positive (P=0.002) or HER2-positive (P<0.0005), but less likely to be treated with breast-conserving surgery (P=0.004). Grade and Ki-67 were lower in IDC-DCIS than in pure IDC (P=0.02), and declined as the DCIS enlarged (P<0.01). Node involvement and lymphovascular invasion in IDC-DCIS increased with the size ratio of IDC to DCIS (P<0.01). A 60-month cancer-specific survival favoured IDC-DCIS over size-matched pure IDC (97.4 vs 96.0%).
IDC co-existing with DCIS is characterised by lower proliferation and metastatic potential than size-matched pure IDC, especially if the ratio of DCIS to IDC size is high. We submit that IDC-DCIS is biologically distinct from pure IDC, and propose an incremental molecular pathogenesis of IDC-DCIS evolution involving an intermediate DCIS precursor that remains dependent for replication on upstream mitogens.
breast neoplasms; pre-invasive; intraductal; Ki-67; carcinogenesis; tumour progression
Ovarian cryopreservation is a promising technique to preserve fertility in women with Hodgkin lymphoma (HL) treated with chemotherapy. Thus, the aim of this study was to examine harvested ovarian tissue for subclinical involvement by HL by morphology/immunohistochemistry, and to define patient and treatment factors predictive of oocyte yield. This was a retrospective analysis of 26 ovarian tissue samples harvested for cryopreservation from women with HL. Histology, immunohistochemistry and follicle density (number mm−3) was examined. Disease status and preharvest chemotherapy details were obtained on 24 patients. The median age was 22 years (range 13–29). Seven of 24 patients had infradiaphragmatic disease at time of harvest. Nine of 20 patients had received chemotherapy preharvest (ABVD (Adriamycin®, Bleomycin, Vinblastine and Dacarbazine)=7, other regimens=2). The seven receiving ABVD showed no difference in follicle density compared to patients not receiving treatment (n=14); (median=1555 vs 1620 mm3 P=0.97). Follicle density measurement showed no correlation with patient age (R2=0.0001, P=0.99). There was no evidence of HL involvement in the 26 samples examined (95% CI=0–11%). In conclusion, subclinical involvement of HL has not been identified in ovarian tissue, even when patients have infradiaphragmatic disease. Furthermore, the quality of tissue harvested does not appear to be adversely affected by patient's age or prior ABVD chemotherapy.
fertility; Hodgkin lymphoma; ovarian cryopreservation
A combination of Adriamycin (a.k.a. Doxorubicin), Bleomycin, Vinblastine, and Dacarbazine (ABVD) is the most commonly used chemotherapy regime for Hodgkin lymphoma. This highly effective treatment is associated with a significant risk of neutropenia. Various strategies are adopted to counter this commonly encountered problem, including dose modification, use of colony stimulating factors, and prophylactic or therapeutic use of antibiotics. Data to support these approaches is somewhat controversial, and in keeping with the paucity of definitive evidence, there is a wide disparity in the management of neutropenia in patients receiving ABVD chemotherapy. This paper summarizes the evidence for managing ABVD-related neutropenia during the treatment of Hodgkin lymphoma.
Myelotoxicity during initial cycles of chemotherapy for Hodgkin lymphoma is associated with better outcome, supporting the concept of individualised dosing based on pharmacodynamic end points to optimise results. This study was performed to identify the maximum tolerated dose (MTD) of doxorubicin within cycles 1–3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Circulating biomarkers of response (nucleosomal DNA, nDNA) and epithelial toxicity (Cytokeratin 18, CK18) were also measured.
Dose escalation of doxorubicin in cycles 1–3 ABVD supported by pegfilgrastim was performed on a six-patient cohort basis (35, 45 and 55 mg m–2) with doxorubicin reduced to 25 mg m–2 or omitted in cycles 4–6 to maintain cumulative exposure of 103–130% standard ABVD. BVD was given at standard doses throughout. Six additional subjects were recruited at the MTD.
Twenty-four subjects were recruited. Dose-limiting toxicities (DLTs) of grade 3 neuropathy, pneumonitis, palmar-plantar erythema and neutropenic infection were observed at 55 mg m–2, so 45 mg m–2 was declared the MTD. In patients who subsequently experienced DLT at any time, large increases in CK18 were seen on day 3 of cycle 1 ABVD.
Escalated ABVD incorporating doxorubicin at 45 mg m–2 in cycles 1–3 can be delivered safely with pegfilgrastim support. Circulating cell death biomarkers may assist in the development of future individualised dosing strategies.
Hodgkin lymphoma; ABVD chemotherapy; cell death biomarkers; phase I
The mechanisms responsible for chemoresistance in patients with refractory classical Hodgkin lymphoma (CHL) are unknown. ATP-binding cassette (ABC) transporters confer multidrug resistance in various cancers and ABCC1 overexpression has been shown to contribute to drug resistance in the CHL cell line, KMH2.
We analyzed for expression of five ABC transporters ABCB1, ABCC1, ABCC2, ABCC3 and ABCG2 using immunohistochemistry in 103 pre-treatment tumor specimens obtained from patients with CHL. All patients received first-line standard chemotherapy with doxorubicin (Adriamycin®), bleomycin, vinblastine, and dacarbazine (ABVD) or equivalent regimens. ABCC1 was expressed in Hodgkin and Reed-Sternberg (HRS) cells in 16 of 82 cases (19.5%) and ABCG2 was expressed by HRS cells in 25 of 77 cases (32.5%). All tumors were negative for ABCB1, ABCC2 and ABCC3. ABCC1 expression was associated with refractory disease (p = 0.01) and was marginally associated with poorer failure-free survival (p = 0.06). Multivariate analysis after adjusting for hemoglobin and albumin levels and age showed that patients with CHL with HRS cells positive for ABCC1 had a higher risk of not responding to treatment (HR = 2.84, 95%, CI: 1.12-7.19 p = 0.028).
Expression of ABCC1 by HRS cells in CHL patients predicts a higher risk of treatment failure and is marginally associated with poorer failure-free survival using standard frontline chemotherapy regimens.
Classical Hodgkin lymphoma; ABCC1; ATP binding cassettes; Immunohistochemistry
Interdigitating dendritic cell sarcoma (IDCS) is a very rare disease around the world and its prognosis is known to be aggressive. This reports a case diagnosed as IDCS of the axillary region treated in Soonchunhyang University Hospital. A 57-year-old female visited Soonchunhyang University Hospital with a left axillary mass. The mass was hard and fixed. Computed tomography observed a 7 cm lymph node at the left axilla, and core biopsy suspected sarcoma. In another study, there was no specific finding except the axillary lesion. Left axillary lymph node dissection (level I, II) was conducted and the pathologic report finally showed IDCS. The patient was treated with only radiotherapy and followed up without recurrence for 13 months up to now. IDCS is a very rare sarcoma that is hard to diagnose and progresses fast. Thus, treatment is very difficult. Proper treatment can be better established after more experiences.
Interdigitating dendritic cell sarcoma; Axilla
Interdigitating dendritic cell sarcoma (IDCS) and histiocytic sarcoma (HS) are two distinct rare hematolymphoid neoplasms, and HS derived from a likely pre-existing IDCS has never been reported in the English literature. Diagnosis of such entities in excised specimens is difficult, but becomes more difficult with the scant amount of materials obtained with fine needle aspiration (FNA) and core needle biopsy. Here we present an interesting and unique case of an IDCS located within a mesenteric mass, which was initially diagnosed as IDCS from the cytology of FNA and core needle biopsy specimens. After brief chemotherapy, the patient again developed abdominal pain, and a HS was diagnosed based on the excised segmental small intestinal specimen. While the exact relationship between the IDCS and HS cannot be ascertained, it is most likely that the HS is derived from the IDCS, although co-existing HS in addition to IDCS from the cytology specimen cannot be completely ruled out.
Interdigitating dendritic cell sarcoma; histiocytic sarcoma; fine needle aspiration
Primary mediastinal choriocarcinoma is a rare extragonadal germ cell malignancy. We describe the first case of a patient who developed mediastinal choriocarcinoma after treatment for Hodgkin lymphoma (HL). A 25-year-old man with classic HL, nodular sclerosis subtype, underwent treatment with splenectomy followed by radiation therapy. Unfortunately, his disease relapsed with a paraspinal mass, and he was subsequently treated with MOPP (mechlorethamine, Oncovin, procarbazine, and prednisone) alternating with ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). He achieved a complete remission after 6 cycles. Ten years after treatment, the patient presented with a persistent cough, haemoptysis, right supraclavicular lymphadenopathy, and weight loss. His chest X-ray showed opacification of the lower right hemithorax with a widened mediastinum. Given unresponsiveness to several antibiotics and lack of evidence for lung volume loss, there were concerns over lung infiltration with relapsed lymphoma. Transbronchial fine needle aspiration biopsy suggested recurrence of his HL. MOPP alternating with ABVD was again given. Due to disease progression, brachytherapy as well as a cocktail of dexamethasone, cytarabine, and cisplatin were also tried. However, on a subsequent excisional lymph node biopsy, it turned out that the tumour was in fact choriocarcinoma and not relapsed HL. Unfortunately, despite aggressive therapy, the patient's disease rapidly progressed, and he died within 2 weeks.
Germ cell tumour; Choriocarcinoma; Hodgkin lymphoma; Mediastinal tumour
The simultaneous presentation of the Hodgkin lymphoma and multiple myeloma in the absence of prior chemotherapy or radiation is very rare. Here, we discuss a 72-year-old patient who initially presented with generalized pruritis. Workup led to a diagnosis of multiple myeloma which progressed and required treatment. As part of his pretreatment workup, an MRI was performed to evaluate skeletal lesions. This revealed diffuse and bulky adenopathy which was confirmed by PET. A biopsy of an axillary node was consistent with the nodular sclerosing type Hodgkin lymphoma. He was treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy × 6 resulting in complete resolution of his adenopathy and pruritis as well as improvement in his myeloma.
Assessment of patients prior to cytotoxic chemotherapy usually includes absolute neutrophils count. Other cellular markers of susceptibility to infection as well as immunocompetence include the T Helper lymphocyte count. In cancer patients, decrease in these lymphocytes has been observed to be associated with decreased overall survival.
To assess the degree of CD4 lymphopenia encountered during cytotoxic chemotherapeutic treatment for cancer and evaluate the differences observed for the various drug combinations.
Subjects and Methods:
Eighty patients with various histologically diagnosed malignancies had their CD4 lymphocyte counts carried out at days 0 and 12 of the first cycle of their various chemotherapeutic regimens. They were adult patients who had been diagnosed with breast cancer 36/80 cases (45%), non-Hodgkin's lymphoma 8/80 cases (10%), Hodgkin's lymphoma 13/80 cases (16.3%), multiple myeloma 7/80 cases (8.8%), colorectal carcinoma 6/80 cases (7.5%), and other malignancies 10/80 cases (12.5%). CD4 lymphocyte count was done using the Partec Cyflow® 2000 CD4 cell counter, and their socio-demographic data of the patients were assessed using a questionnaire.
The mean (sd) CD4 lymphocyte count pre- and post-chemotherapy was observed to be 567 (341) cells/μLand 349 (207) cells/μL while the median values were 454 cells/μLand 349 cells/μL respectively. There were significant differences in CD4 lymphocyte counts after chemotherapy compared to the pre-chemotherapy values.
Epirubicin combinations used in breast cancer patients as well as (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) ABVD regimen used in treatment of Hodgkin's lymphoma were found to be significantly less lymphotoxic than other chemotherapeutic combinations. These drugs or their combinations may be less immunotoxic than other known regimen used for these malignancies.
Cancers; CD4 lymphocyte; Cytotoxic chemotherapy; Immunosuppression
In newly diagnosed patients with Hodgkin lymphoma (HL) the effect of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)-related neutropenia on chemotherapy delivery is poorly documented. The aim of this analysis was to assess the impact of chemotherapy-induced neutropenia (CIN) on ABVD chemotherapy delivery in HL patients.
Data from two similarly designed, prospective, observational studies conducted in the US and the EU were analysed. One hundred and fifteen HL patients who started a new course of ABVD during 2002-2005 were included. The primary objective was to document the effect of neutropenic complications on delivery of ABVD chemotherapy in HL patients. Secondary objectives were to investigate the incidence of CIN and febrile neutropenia (FN) and to compare US and EU practice with ABVD therapy in HL. Pooled data were analysed to explore univariate associations with neutropenic events.
Chemotherapy delivery was suboptimal (with a relative dose intensity ≤ 85%) in 18-22% of patients. The incidence of grade 4 CIN in cycles 1-4 was lower in US patients (US 24% vs. EU 32%). Patients in both the US and the EU experienced similar rates of FN across cycles 1-4 (US 12% vs. EU 11%). Use of primary colony-stimulating factor (CSF) prophylaxis and of any CSF was more common in the US than the EU (37% vs. 4% and 78% vs. 38%, respectively). The relative risk (RR) of dose delays was 1.54 (95% confidence interval [CI] 1.08-2.23, p = 0.036) for patients with vs. without grade 4 CIN and the RR of grade 4 CIN was 0.35 (95% CI 0.12-1.06, p = 0.046) for patients with vs. without primary CSF prophylaxis.
In this population of HL patients, CIN was frequent and FN occurrence clinically relevant. Chemotherapy delivery was suboptimal. CSF prophylaxis appeared to reduce CIN rates.
Autoimmune hemolytic anemia (AIHA) has been associated with chronic lymphocytic leukemia, non-Hodgkin lymphoma, and classical Hodgkin lymphoma, but to the best of our knowledge, the association of AIHA and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) has not been reported previously. A 20-year-old woman presented with conjunctival jaundice, fever, asthenia, and hemoglobin 9.2 g/dL revealing IgG-mediated warm antibody AIHA. Computed tomography (CT) scan and positron-emission tomography (PET) scan showed mediastinal and axillary lymph nodes with increased [18F]-fluorodeoxyglucose uptake. A mediastinal lymph node was biopsied during mediastinoscopy, and NLPHL was diagnosed by an expert hematopathologist. The hemoglobin level declined to 4.6 g/dL. The treatment consisted of four 28-day cycles of R-ABVD (rituximab 375 mg/m2 IV, adriamycin 25 mg/m2 IV, bleomycin 10 mg/m2 IV, vinblastine 6 mg/m2 IV, and dacarbazine 375 mg/m2 IV, each on days 1 and 15). Prednisone was progressively tapered over 10 weeks. After the first chemotherapy cycle, the hemoglobin level rose to 12 g/dL. After the four cycles, PET and CT scans showed complete remission (CR). At the last followup (4 years), AIHA and NLPHL were in sustained CR.
To examine ovarian reserve following chemotherapy in women with Hodgkin’s disease.
The study included nine patients who underwent ovarian tissue cryopreservation (OTCP) prior to chemotherapy consisting of the ABVD regimen (Adriamycin, bleomycin, vinblastine, and dacarbazine) and co-treatment with gonadotropin-releasing hormone agonist (GnRH-a) (Group A), and 13 patients treated by the ABVD protocol only without GnRH-a (Group B). The average age was 25.2 ± 2.7 years for the women in Group A and 31.8 ± 6.8 years for those in Group B.
Six months following the end of chemotherapy, the menstrual cycle resumed in all Group A patients and in four Group B patients who had amenorrhea. Eight Group B patients had regular menses during and after chemotherapy. None of the patients suffered from ovarian failure. Two Group A patients conceived in the first year after completing chemotherapy.
Co-treatment with GnRH-a has little effect on ovarian protection in women with Hodgkin’s disease.
Hodgkin’s disease; Chemotherapy; Ovarian tissue cryopreservation; GnRH-a; Ovarian reserve
The management of classical Hodgkin's lymphoma (CHL) is a success story of modern multi-agent haemato-oncology. Prior to the middle of the twentieth century CHL was fatal in the majority of cases. Introduction of single agent radiotherapy (RT) demonstrated for the first time that these patients could be cured. Developments in chemotherapy including the mechlorethamine, vincristine, procarbazine and prednisolone (MOPP) and Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) regimens have resulted in cure rates of over 80%. Even in relapse, CHL patients can be salvaged with high dose chemotherapy and autologous haematopoietic stem cell transplantation (ASCT). Challenges remain, however, in finding new strategies to manage the small number of patients who continue to relapse or progress. In addition, the young age of many Hodgkin's patients forces difficult decisions in balancing the benefit of early disease control against the survival disadvantage of late toxicity. In this article we aim to summarise past trials, define the current standard of care and appraise future developments in the management of CHL.
Neoplasms of histiocytic and dendritic cells are rare disorders of the lymph node and soft tissues. Because of this rarity, the corresponding biology, prognosis and terminologies are still being better defined and hence historically, these disorders pose clinical and diagnostic challenges. These disorders include Langerhans cell histiocytosis (LCH), histiocytic sarcoma (HS), follicular dendritic cell sarcoma (FDCS), interdigtating cell sarcoma (IDCS), indeterminate cell sarcoma (INDCS), and fibroblastic reticular cell tumors (FRCT). In order to gain a better understanding of the biology, diagnosis, and treatment in these rare disorders we reviewed our cases of these neoplasms over the last twenty five years and the pertinent literature in each of these rare neoplasms. Cases of histiocytic and dendritic cell neoplasms diagnosed between 1989–2014 were identified using our institutional database. Thirty two cases were included in this analysis and were comprised of the following: Langerhans cell histiocytosis (20/32), histiocytic sarcoma (6/32), follicular dendritic cell sarcoma (2/32), interdigitating dendritic cell sarcoma (2/32), indeterminate dendritic cell sarcoma (1/32), and fibroblastic reticular cell tumor (1/32). Median overall survival was not reached in cases with LCH and showed 52 months in cases with HS, 12 months in cases with FDCS, 58 months in cases with IDCS, 13 months in the case of INDCS, and 51 months in the case of FRCT. The majority of patients had surgical resection as initial treatment (n = 18). Five patients had recurrent disease. We conclude that histiocytic and dendritic cell neoplasms are very rare and perplexing disorders that should be diagnosed with a combination of judicious morphology review and a battery of immunohistochemistry to rule out mimics such as carcinoma, lymphoma, neuroendocrine tumors and to better sub-classify these difficult to diagnose lesions. The mainstay of treatment for localized disease remains surgical resection and the role of adjuvant therapy is unclear. In patients with multiple areas of involvement, treatment at tertiary care centers with multimodality treatment is likely needed. Accurate subset diagnosis will contribute to better data as well as treatment outcomes analysis of these rare disorders of adult patients in the future.
dendritic cell tumor; Langerhans cell histiocytosis; histiocytic sarcoma; follicular dendritic cell sarcoma; interdigitating dendritic cell sarcoma; indeterminate dendritic cell sarcoma; fibroblastic reticular cell tumor
Hodgkin’s lymphoma (HL) is one of the few adult malignancies that most frequently presents with a progressive, painless enlargement of the peripheral lymph nodes. A primary osseous presentation of HL, without lymph node involvement, is extremely rare. The present study describes a case of primary multifocal osseous HL in a 22-year-old female. The patient presented with pain in the lumbar-sacral-pelvic area and a prolonged fever. Pathological examination led to a diagnosis of primary multifocal osseous lymphoma, and the patient was subsequently prescribed a course of Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy. Following this, the patient recovered with no pain or fever, and computed tomography identified no further progression. The clinical, radiological and histological features of HL are similar to those of other medical conditions, such as tuberculosis and eosinophilic granuloma. Furthermore, in rare cases, HL may even occur in combination with multiple myeloma. This makes it difficult to diagnose the condition, which often leads to a delay in treatment. Clinicians should not ignore HL when it manifests in the unusual primary osseous form.
Hodgkin’s lymphoma; bone; diagnosis
The aim of the present study was to investigate brain glucose metabolism in patients with Hodgkin disease (HD) after diagnosis and during chemotherapy treatment. Following the administration of first-line doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy, 74 HD patients underwent 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography brain scans, both baseline (PET0) and interim (PET2) at the Department of Biomedicine and Prevention, University of Rome Tor Vergata (Rome, Italy). Fifty-seven patients were further evaluated 15±6 days after four additional cycles (PET6). Furthermore, a control group (CG) of 40 chemotherapy-naïve subjects was enrolled. Differences in brain 18F-FDG uptake between the CG, PET0, PET2 and PET6 scans were analyzed using statistical parametric mapping. Compared with the PET0 and CG scans, the PET2 scan demonstrated a higher metabolic activity in Brodmann area (BA) 39, and a metabolic reduction in BA 11 bilaterally and in left BA 32. All of these changes disappeared at PET6. The results of the present study indicate that ABVD chemotherapy has a limited impact on brain metabolism.
adriamycin; bleomycin; vinblastine and dacarbazine; chemotherapy; chemobrain; Hodgkin disease; positron emission tomography
A 24-year-old African American female (L.R.) with a history of smoking and gestational diabetes was diagnosed with Hodgkin lymphoma. She received multiple chemotherapies, including six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), followed by radiation therapy to left inguinal areas for a total of 30.6 Gy in 17 fractions; she obtained complete remission. Two years later, L.R. had disease relapse in the mediastinum and received two cycles of ESHAP (etoposide, methylprednisolone, high-dose cytarabine, cisplatin) followed by etoposide and ifosfamide. She then received BEAM (carmustine, etoposide, cytarabine, and melphalan) as a conditioning regimen and underwent autologous bone marrow transplant. Her post-transplant course was complicated by cytomegalovirus antigenemia, aspergillus pneumonia, and congestive heart failure with left ventricular ejection fraction (LVEF) of 20%–25%. She was treated with an ACE inhibitor (lisinopril) and a beta-blocker (carvedilol) with improvement of her LVEF to 30%–35%. A follow-up chest x-ray showed an increase in the size of the anterior mediastinal adenopathy suspicious for relapse of lymphoma, and at the same time she was also found to be 5 weeks pregnant.
Given her cardiomyopathy, significant obesity, poorly controlled diabetes, and cancer recurrence, L.R. was advised by her gynecologist that the pregnancy was very high risk and might not be viable. The oncologists advised her to terminate the pregnancy within the first trimester, as she needed salvage radiotherapy treatment to the mediastinum and chemotherapy treatments that might endanger the fetus. However, the patient decided to continue with the pregnancy. A multidisciplinary team—which included a cardiologist, oncologist, high-risk obstetrician, pharmacist, and nurse practitioner—was then involved to provide care during the pregnancy. A social worker was also solicited to help with home and financial issues because L.R. was a single mother with a 2-year-old son.
L.R. was treated with carvedilol and furosemide, with monthly cardiology clinical follow-up during the first and second trimesters, then every 2 weeks starting with the 28th week, and weekly thereafter until delivery. Between visits, she notified the clinic for symptoms of heart failure exacerbation and was seen as necessary. The possible in utero effects of both medications were discussed with the patient. L.R. had a normal uncomplicated pregnancy and delivered a 6-pound, 10-ounce healthy boy at 39 weeks via vaginal delivery and was discharged home 2 days later.
A week after delivery, L.R. presented to the cardiology clinic in good spirits and was excited to show pictures of her newborn baby. She had no cardiac complaints and the repeat echocardiogram showed an unchanged LVEF of 30%–35%.
Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare malignancy derived from professional antigen presenting cells. This report describes a case of IDCS arising in the salivary gland associated lymphoid tissue of the parotid gland of a 51 year woman, presenting with a painless neck swelling. Histologically, sheets of S100+/Ccd68+/CD45+/CD34−/CD1a− spindle cells were surrounded with an inflammatory infiltrate with no evidence of B or T cell clonal proliferations. No evidence of either human herpesvirus 8 or Epstein-Barr virus could be detected by quantitative polymerase chain reaction in the tumour cells with serological evidence of previous Epstein-Barr virus infection. The patient remains well and disease free 24 months after presentation without specific treatment.
interdigitating dendritic cell sarcoma; Kaposi’s sarcoma associated herpes virus; Epstein-Barr virus
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma (HL), and is a rare disease manifestation in the adrenal gland, which is difficult to be diagnosed and treated. In the present study, we report a case of primary adrenal NLPHL in a 36-year-old male patient. The patient was without specific clinical signs and the definitive diagnosis was achieved by histological study. The patient underwent a laparoscopic left adrenalectomy and chemotherapy regimen of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). There is no standard treatment for adrenal NLPHL and therefore, treatment is based on that for other types of NLPHL, which includes radiotherapy and ABVD chemotherapy. Given the rarity of this disease, there are limited experiences with regard to its diagnosis and treatment. This study is useful for the differential diagnosis and treatment of adrenal masses.
nodular lymphocyte-predominant Hodgkin lymphoma; adrenal gland; histopathology