Role of Hematotoxicity and Sex in Patients With Hodgkin's Lymphoma: An Analysis From the German Hodgkin Study Group

Klimm, Beate; Reineke, Thorsten; Haverkamp, Heinz; Behringer, Karolin; Eich, Hans Theodor; Josting, Andreas; Pfistner, Beate; Diehl, Volker; Engert, Andreas

doi:10.1200/jco.2005.205.60

Cited by 64 publications

(39 citation statements)

References 39 publications

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“…Finally and ironically, we may be limited by our success. Perhaps the strongest evidence comes from HL, 23 where the numbers are large and studies have been done. Here, it may be precisely that outcomes are generally so good that there is a lack of incentive to test the most basic of assumptions regarding the use of long-established regimens.…”

Section: Discussionmentioning

confidence: 99%

“…In HL, females were reported to experience both greater toxicity and better survival than males, and the degree of neutropenia correlated with eventual outcome. 23 Females experience worse toxicity than males following treatment for colorectal cancer. [24][25][26] Although not linked to pharmacodynamic measures, better outcomes for females have also been described for ES 27,28 and OS.…”

Section: Discussionmentioning

confidence: 99%

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Gender‐specific activity of chemotherapy correlates with outcomes in chemosensitive cancers of young adulthood

Khamly

Thursfield

Fay

et al. 2009

Intl Journal of Cancer

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Good evidence indicates that adolescents and young adults (AYAs) with cancer do badly compared with children with similar cancers. The reasons are poorly understood. Australian registry data on 14,824 cancers of adolescence and young adulthood seen between 1982 and 2002 were reviewed. A detailed substudy of clinical characteristics was analyzed from 179 AYAs with Hodgkin lymphoma (HL), Ewing sarcoma (ES) or osteosarcomas (OS) treated at a single institution. Despite significant improvements in survival for both groups over the period in question, for acute lymphoblastic leukaemia, rhabdomyosarcoma, ES, OS and HL, survival for AYAs was worse than for children. For ES, OS and HL, the survival gap occurred almost entirely in males (Hazard ratios compared with female AYAs of 1.8 [p < 0.01], 1.4 [p = 0.03] and 1.5 [p < 0.01] respectively). Survival outcomes from ES, OS and HL for female AYAs were not significantly different from children of either sex. For brain tumors and thyroid cancers, which are primarily treated surgically, there were no gender‐related differences in outcomes. Although no differences in tumor stage or compliance were identified, male AYAs experienced less toxicity and lower response rates to chemotherapy (p = 0.008). Young males account almost entirely for excess mortality from chemosensitive cancers of adolescence and young adulthood compared to children, which may be due to relative underdosing with current chemotherapy dosing algorithms. © 2009 UICC

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Gender‐specific activity of chemotherapy correlates with outcomes in chemosensitive cancers of young adulthood

Khamly

Thursfield

Fay

et al. 2009

Intl Journal of Cancer

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“…Because myelosuppression is reflected in number and depth of episodes of neutropenia, and female gender correlates with increased sensitivity to marrow suppression, these studies typically demonstrate that women have more episodes of neutropenia and deeper and more prolonged nadirs in neutrophil counts compared with men given the same doses of chemotherapy. 15 Because depth and length of myelosuppression reflect biological potency of chemotherapy agents, patients who experience greater myelosuppression (in this case, women) have better outcomes, reflecting the more effective dosing of the chemotherapy.…”

Section: Risk Factors Intrinsic To the Patientmentioning

confidence: 99%

Risk assessment in the management of newly diagnosed classical Hodgkin lymphoma

Connors

2015

Blood

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Treatment of Hodgkin lymphoma is associated with 2 major types of risk: that the treatment may fail to cure the disease or that the treatment will prove unacceptably toxic. Careful assessment of the amount of the lymphoma (tumor burden), its behavior (extent of invasion or specific organ compromise), and host related factors (age; coincident systemic infection; and organ dysfunction, especially hematopoietic, cardiac, or pulmonary) is essential to optimize outcome. Elaborately assembled prognostic scoring systems, such as the International Prognostic Factors Project score, have lost their accuracy and value as increasingly effective chemotherapy and supportive care have been developed. Identification of specific biomarkers derived from sophisticated exploration of Hodgkin lymphoma biology is bringing promise of further improvement in targeted therapy in which effectiveness is increased at the same time off-target toxicity is diminished. Parallel developments in functional imaging are providing additional potential to evaluate the efficacy of treatment while it is being delivered, allowing dynamic assessment of risk during chemotherapy and adaptation of the therapy in real time. Risk assessment in Hodgkin lymphoma is continuously evolving, promising ever greater precision and clinical relevance. This article explores the past usefulness and the emerging potential of risk assessment for this imminently curable malignancy.

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“…The GHSG showed that severe leucopenia (defined as WHO grade 3-4) during HL therapy was associated with superior survival (Klimm et al, 2005). Among 4626 patients, women had more frequent severe leucopenia, similar infection rate, and improved freedom-from-treatment failure (FFTF) compared with men.…”

Section: Discussionmentioning

confidence: 99%

G‐CSF is not necessary to maintain over 99% dose–intensity with ABVD in the treatment of Hodgkin lymphoma: low toxicity and excellent outcomes in a 10‐year analysis

Evens

Cilley

Ortiz³

et al. 2007

Br J Haematol

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SummaryDose–intensity of chemotherapy is important in the treatment of Hodgkin lymphoma (HL) and granulocyte‐colony stimulating factor (G‐CSF) is commonly used to maintain it. We reviewed all newly diagnosed HL patients who were treated at our institution between 1996 and 2005. Fifty‐nine patients received adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy with no dose reductions, treatment delays, and without G‐CSF, regardless of absolute neutrophil count (ANC). The median ANC on all ABVD treatment days (n = 658) was 0·925 × 109/l, and was <0·5 × 109/l on 26% of treatment days. Median normalised ABVD dose–intensity was 99·1% (range, 93–100%) and median cycle duration was 28·2 d. Incidence of bleomycin lung toxicity was 1·6%, 0·44% treatments were complicated by febrile neutropenia, and no secondary malignancies have occurred (median follow‐up 48 months; range, 11–130 months). Five‐year event‐free (EFS) and overall survival (OS) were 92·9% and 97·4% respectively. Furthermore, the 5‐year EFS and OS (87·4% and 94·1% respectively) for advanced stage patients compared favourably with a similar ABVD patient group who received routine prophylactic G‐CSF (n = 23) with EFS 80·0% and OS 91·3% (P = 0·46 and 0·67 respectively). Our experience suggests that ABVD may be safely and effectively administered at >99% dose–intensity without G‐CSF support, regardless of the ANC.

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Role of Hematotoxicity and Sex in Patients With Hodgkin's Lymphoma: An Analysis From the German Hodgkin Study Group

Abstract: The protective role of severe leucopenia suggests the testing of a more individualized therapy. In future trials, this therapy may be tailored in a response-adapted manner depending on the individual toxicity profile within the first cycles.

Cited by 64 publications

References 39 publications

Gender‐specific activity of chemotherapy correlates with outcomes in chemosensitive cancers of young adulthood

Gender‐specific activity of chemotherapy correlates with outcomes in chemosensitive cancers of young adulthood

Risk assessment in the management of newly diagnosed classical Hodgkin lymphoma

G‐CSF is not necessary to maintain over 99% dose–intensity with ABVD in the treatment of Hodgkin lymphoma: low toxicity and excellent outcomes in a 10‐year analysis

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