Clinical indications and biological mechanisms of splenic irradiation in chronic leukaemias and myeloproliferative disorders.

Splenic irradiation (SI) was the first efficient treatment for chronic leukaemia, but with the emergence of effective drugs its use has been more and more restricted to advanced cases presenting with splenomegaly. But in selected patients who are not responsive or not suitable to drug treatment, SI may offer still an effective, low toxic and cost-effective palliative modality. Eight studies of SI in chronic lymphatic leukaemia (CLL) including 198 patients, six reports about SI in prolymphocytic leukaemia (PLL), including 18 patients, one study and six case reports about SI in hairy cell leukaemia (HCL) and nine studies about SI in myeloproliferative disorders has been analyzed. In CLL, symptoms of splenomegaly have been improved in 50-87% of all patients with overall doses between 4 and 10 Gy in mostly 1-Gy fractions. PLL seems to be more resistant to SI with a median response rate of 66%. Casuistic reports described also efficacy of SI in HCL patients using similar radiation schedules. Symptomatic relief is also provided by SI in myeloproliferative disorders using lower overall doses between 1 and 9 Gy with small single fractions of 0.25 Gy (median). Acute toxicity was low in lymphoid disorders, but higher in myeloproliferative disorders with severe cytopenia in 10-30% of all cases, indicating the need for a cautious fractionation schedule. Interestingly, even complete systemic remissions after SI in all types of lymphoproliferative disorders have been described. Different mechanisms underlying SI such as direct cell kill, immune modulation via changes in lymphocyte subsets or cytokine induction or "radiotherapeutic" splenectomy with high doses are discussed.

Splenic irradiation for prolymphocytic leukemia: is it preferable as an initial treatment or not?

We describe a case of B-cell prolymphocytic leukemia (PLL) successfully treated with splenic irradiation (SI). A 69-year-old woman was admitted to our hospital because of massive splenomegaly and leukocytosis. Peripheral blood showed hemoglobin (Hb) 7.4 g/dl, platelets 48 x 10(9)/l and white blood cells (WBC) 50.3 x 10(9)/l with 90% prolymphocytes. Bone marrow was hypercellular with 60% prolymphocytes. Surface marker analysis revealed that prolymphocytes were positive for CD20, CD22, FMC7, HLA-DR and surface immunoglobulin (mu, delta and lambda), but negative for CD5 and mouse erythrocyte rosette. A diagnosis of B-cell PLL was made. SI (1.5 Gy x 4/week, total dose 19.5 Gy) was chosen for the treatment and a remarkable response was achieved immediately after the first irradiation. Finally, a single course of SI induced complete remission without any significant side effect. One year after the SI, she showed no splenomegaly and almost normal peripheral blood cell count (Hb 11.2 g/dl, platelets 100 x 10(9)/l, WBC 3.6 x 10(9)/l with 71% neutrophils and no prolymphocyte). She has been well for more than 24 months. This case showed that SI may remain valuable for an initial course of PLL treatment.

Prolymphocytic leukemia: a very satisfactory response to treatment with recombinant interferon alpha.

We report the case of a patient with prolymphocytic leukemia in whom a lengthy survival of 5 years was observed after treatment with splenic irradiation and chemotherapy. The patient obtained a surprising improvement with a significant reduction in the absolute count of the prolymphocytes and considerable reduction in splenomegaly after 3 months' therapy with interferon alpha.

Splenic irradiation as primary therapy for prolymphocytic leukemia.

A patient with prolymphocytic leukemia (PLL), a lymphoproliferative disorder that carries a poor prognosis, is presented. The disease was diagnosed at an early stage and treatment could be delayed for four years. When massive, painful splenomegaly developed, splenic irradiation (SI) was chosen as the primary form of therapy and an excellent systemic response could be achieved. Our observation is in agreement with preliminary studies, which advocate SI as the primary form of therapy in PLL. Furthermore, it is emphasized that an early diagnosis of PLL is necessary to establish its true course and that the prognosis may be better than originally thought.