Hodgkin's lymphoma, [s8]uncommon

This disease of the reticuloendothelial system occurs all over the world, and is unusual in having a bimodal age distribution curve, with a peak in teenagers, and another in patients over the age of 50.

A patient with Hodgkin's disease may present with: (1) Enlarged, discrete, painless, rubbery lymph nodes in his neck (60%), mediastinum (15%), abdomen or groin (15%), or axilla, (10%). (2) Weight loss. (3) Fever which may simulate an infection and is classically of the Pel[nd]Ebstein type (up for 3 to 5 days, followed by a remission of a few days, and then fever again).

The various histological types each have their own prognosis: (1) Predominantly lymphocytic (15% of cases). (2) Nodular sclerotic (50%). (3) Mixed cellularity (20%). (3) Lymphocyte-depleted (15%). Under the age of 30 the nodular sclerotic type predominates; in older patients the lymphocytic and mixed cellularity types are more common.

Initially, only his lymph nodes are involved. Later, the disease spreads to his spleen, marrow, and liver. Late complications include: obstruction to his trachea and bronchi, pleural effusion, biliary obstruction causing jaundice, cord compression, lytic and/or sclerotic bone deposits, anaemia, and infections, especially in debilitated patients.

Untreated cases deteriorate, many only slowly, and die in a few months to a few years. Radiotherapy and chemotherapy cure some of them, and cause many long-term remissions. Chemotherapy is so successful in early cases that only Burkitt's lymphoma should have greater priority.

HODGKIN'S LYMPHOMA DIAGNOSIS. Examine all accessible lymph nodes. Note the nature and size of all enlarged ones. Feel for enlargement of the patient's liver and spleen; assess his weight loss.

X-RAYS. Look for widening of his mediastinum and enlargement of his hilar lymph nodes.

SPECIAL TESTS. Do a total and differential white count, and count his platelets.

Before you start cytotoxic drugs: (1) Establish the diagnosis by biopsy. (2) Look for signs of infection; culture his urine, and measure his blood urea.

THE DIFFERENTIAL DIAGNOSIS includes the common causes of lymph node enlargement, with or without fever: non-specific hyperplasia, tuberculous lymphadenitis (29.2), ARC (AIDS-related complex), non-Hodgkin's lymphoma (32.5), chronic lymphatic leukaemia, and infectious mononucleosis.

Suggesting Hodgkin's lymphoma[md]painless, non- tender, rubbery discrete nodes with a uniform light greyish- yellow ''fish-flesh' cross-section.

Suggesting tuberculosis [md]enlarged nodes which are matted together, and occasionally tender; caseous areas on cross section.

STAGING AND RESPONSE. Here is the method of staging and the response rate (as measured by the failure of the disease to progress), that you can expect with radiotherapy, or the ''MOPP' cytotoxic regime described below, which are about equally effective. The 5-year survival rate also depends on the histological grading, and for all stages together on ''MOPP', it is 95% for ''lymphocyte predominant', 75% for ''nodular sclerotic', 55% for ''mixed cellularity', and 35% for ''lymphocyte depleted'.

Stage One A single group of nodes. Survival rates, 5 years 90%, 10 years 90%.

Stage Two Two or more groups of nodes on the same side of the diaphragm. Survival rates, 5 years 80%, 10 years 75%.

Stage Three Enlarged nodes above and below the diaphragm. Survival rates, 5 years 60%, 10 years 50%.

Stage Four Disseminated disease. Survival rates, 5 years 45%, 10 years 10%.

E, an extranodal site. A, absence of systemic symptoms and signs, such as fever. B, fever ([mt]38.5[de]C), or weight loss [mt]10%. Examples. IE, a single extranodal site, such as the spleen. IIE, enlarged nodes and extranodal disease on the same side of the diaphragm (except the liver). IIIE, enlarged nodes, and extranodal disease on both sides of the diaphragm.

RADIOTHERAPY will probably be impossible, so you will have to rely on chemotherapy. If you can refer him for radiotherapy, here are the relative indications for it.

Stages One and Two. Radiotherapy and chemotherapy give comparable results, but radiotherapy has fewer side- effects.

Stage Three. Radiotherapy is difficult because a wide area has to be irradiated; chemotherapy is better.

Stage Four. Radiotherapy is impractical, give chemotherapy.

PREPARATION. Prepare him for chemotherapy as in Section 32.2.

''MOPP' [s7]A COMBINED DRUG REGIME ''MOPP' (''Mustine', ''Oncovin', procarbazine, and prednisolone), is a well established regime.

Nitrogen mustard (''Mustine') 6 mg/m['2], maximum dose 12.5 mg, intravenously, on days 1 and 8. If necessary cyclophosphamide can replace the ''Mustine' in MOPP at a dose of 1 g/m['2].

Vincristine (''Oncovin') 1.4 mg/m['2], maximum dose 2.0 mg, intravenously on days 1 and 8.

Procarbazine 100 mg/m['2], maximum dose 200 mg, orally on days 1 to 14.

Prednisolone 40 mg/m['2] maximum dose 60 mg, orally on days 1 to 14.

GIVING THE DRUGS. Sedate him with 25 to 75 mg of chlorpromazine orally. Two hours later give the ''Mustine' and ''Vincristine' intravenously. Give the freshly made up preparations into a freely running intravenous drip. Or, give them by bolus intravenous injection, slowly and well-diluted, with the second drug 20 minutes later.

CAUTION ! A leak, especially of ''Mustine', will cause a severe local reaction, so give it with the greatest possible care.

Repeat the course on day 28 (after a 4 week interval). Give up to 6 courses, and then see him monthly. Measure his total and differential white count, his haemoglobin and his platelets weekly. Assess his response on the Karnofsky scale (32.1), and by measuring his nodes and spleen with a tape measure.

If his white count falls below 2500 [gm]l, give half the dose of ''Mustine' and procarbazine.

SINGLE DRUG REGIMES. If you don't have the drugs for ''MOPP', you can give him cyclophosphamide 1.5 g/m['2] intravenously, repeated every 3 to 4 weeks, for six doses. Or ''Mustine', or vincristine or procarbazine, in the same doses as for ''MOPP'. These single drugs have about a 40 to 50% response rate, which is not as good as ''MOPP', but is much better than nothing.

DIFFICULTIES [s7]WITH ''MOPP' If, as is likely, there are TOXIC EFFECTS, anticipate and manage them like this.

Nausea and vomiting from the ''Mustine' and the procarbazine seldom last for more than 8 hours. Minimize them by giving chlorpromazine beforehand. They may limit the dose of procarbazine you can use, but he usually becomes more tolerant with repeated doses.

Leucopenia from the ''Mustine' and the procarbazine; the latter may also cause anaemia and thrombocytopenia, which may present late.

Local irritation and ulceration occur if the drug leaks from a vein. Local irritation and ulceration (and peripheral neuritis) will not be helped by delaying the drugs. They take far too long to recover. If they are a major problem reduce the dose. Thrombophlebitis is also seen.

Peripheral neuritis, from the vincristine and the procarbazine, present as pain, weakness, loss of sensation, and hot palms and soles of the feet. These effects are usually reversible if the drug is stopped, but take time. In the next course of vincristine and procarbazine give only half the dose. Or, if pain is a problem, stop them at least temporarily. Stop them if there is any objective muscle weakness on dorsiflexion of his foot. Unfortunately, the response rate will then be much lower.

Ileus from the vincristine. Delay the next dose until he is better, and halve it on restarting.

Stomatitis and diarrhoea from the procarbazine (uncommon). Halve the dose.

Lethargy, hyperexcitability, and fits (uncommon) from the procarbazine. Stop the drug.

The side-effects of steroids from the prednisolone[md]raised blood pressure, moon face, increased weight, peptic ulceration, the unmasking of diabetes, etc. These are seldom sufficient to stop the drug, or to reduce the dose.

If he RELAPSES the possibilities are: (1) radiotherapy. (2) A second course of ''MOPP' with a response rate of about 50%. Or, (3) an alternative regime ''ABVD' (not described here) for which you will have to refer him.