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Drug therapy of Hodgkin's lymphoma

The treatment of classic Hodgkin's lymphoma and nodular lymphocyte-rich Hodgkin's lymphoma are somewhat different. 

Classic Hodgkin's lymphoma

The disease frequently presents in stage I or II above the diaphragm. Patients without risk factors have until the late 90ies been given radiation therapy alone (mainly mantle field irradiation). Patients with risk factors have been given combined chemotherapy and the same radiation fields as patients without risk factors.

The large fields that have been used in the treatment of HL in previous decades may to a large degree explain the high incidence of secondary cancer, cardiovascular diseases and some other late effects in survivors after HL.

Today state of the art therapy for HL internationally combines 2-6 chemotherapy courses with smaller radiation fields for stages I and II.

Treatment for stage III and IV is based on chemotherapy, in some cases supplemented with a smaller radiation field.

Early stage classic Hodgkin's lymphoma (stages IA and IIA)

For localized classic Hodgkin's lymphoma in stages IA or IIA, the treatment program developed by the Nordic Lymphoma Group (1999) is followed. Two (patients without risk factors) to four courses (patients with risk factors) of the ABVD regimen are given in addition to modified involved field radiation therapy 20 Gy (patients without risk factors) or 29.75 Gy (patients with risk factors). The number of courses are determined based on the extent of risk factors, which are given below on the flow chart in the nordic protocol.

Supradiaphragmatic disease

Without risk factors

With risk factors (at least 1)

Non-bulky disease

Bulky disease

< 3 lymph node regions involved

2 non-neighboring regions

ESR < 50

³ 3 lymph node regions involved
 

ESR ³ 50

Chemotherapy, 2 courses ABVD + modified involved field
radiotherapy, 20 Gy

Chemotherapy, 4 courses ABVD + modified involved field
radiotherapy, 29.75 Gy

 

Infradiaphragmatic disease   

Without risk factors

With risk factors (at least 1)

Non-bulky disease

Central/pelvic localization

Lymph nodes in the groin alone (stage IA)

IIA

ESR < 50

Lymph nodes in the groin (stage IA) and ESR ³ 50

 

Bulky disease

Chemotherapy, 2 courses ABVD + modified involved field
radiotherapy, 20 Gy

Chemotherapy, 4 courses ABVD + modified involved field
radiotherapy, 29.75 Gy

Advanced classic Hodgkin's lymphoma (stages IIB – IV)

For advanced classic Hodgkin's lymphoma in stages IIB - IV, combination chemotherapy is given and is sometimes supplemented with radiation therapy to 29.75 Gy to areas considered at risk for later relapse (intital bulky sites, residual masses). Until recently, the ABVD regiment has been the gold standard for treating patients with advanced Hodgkin's lymphoma in many countries. Based on results from a three-armed randomized phase III study directed by the German Hodgkin group where COPP/ABVD, BEACOPP standard, and BEACOPP dose-escalated is compared, Norway has changed the treatment scheme somewhat. This applies to patients with advanced disease and poor prognosis (four or more risk factors according to IPS). These patients are given 2 courses of dose-escalated BEACOPP followed by 6 courses of standard BEACOPP.

Nodular lymphocyte-rich Hodgkin's lymphoma

First line treatment is almost always given with the intent to cure patients with nodular lymphocyte-rich Hodgkin's lymphoma.

In 2011, the treatment for early stage disease (I-IIA) was modified to be identical to the algorithm presented above for classical Hodgkin lymphoma. For advanced stages (IIB-IV) 6-8 courses o ABVD is recommended, and Rituximab is added to day 1 of each course. In the rare case of high risk patients with an IPS over 4 or higher, BEACOPP may be warranted, and again one may consider to add Rituximab.

Chemotherapy for patients over 60 years of age 

The prognosis for Hodgkin's lymphoma is more serious after 60 years of age. The reason for this may be that many elderly patients were previously given the LVPP regimen which gave unacceptable hematological toxicity for this age group. ABVD, which has been the standard in recent years is better tolerated. Still, the treatment program for elderly patients is different from that for younger patients with a more cautious and individualized plan depending on health status and other complicating diseases.

The CHOP regimen has been tested thoroughly on elderly patients with non-Hodgkin's lymphoma and has been used for patients over 60 years with Hodgkin's lymphoma. For localized disease, radiotherapy alone in certain cases is recommended, depending on the condition of the patient and disease localization.

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