Bone marrow myelofibrosis resulting in extramedullary hematopoiesis: primary myeloid metaplasia; or secondary to CML, polycythemia vera, or essential thrombocythemia
Immune thrombocytopnia (ITP)
Hypersplenism: typically seen as cytopenia caused by splenomegaly (e.g. portal hypertension)
Disease-associated side effects (wt. loss, night sweats, low grade fever) often improve, but generally not primary indications
Not likely to be effective in improving disease-related cytopenias (may in fact exacerbate them)
Direct effect on radiosensitive extramedullary hematopoietic tissue or infiltrating lymphocytes
Destruction of hematopoietic precursors residing or traversing the spleen
Early and marked reduction in colony-forming granulocyte macrophages, persisting >1 month
A systemic effect and sometimes peripheral blood and bone marrow complete remissions (CRs) observed in several clinical situations
Mechanism is not clear, but could involve direct RT-induced killing of splenic neoplastic clls, immune modulation via proportional changes in lymphocytes subsets and increased anti-tumor activity, RT-induced release of cytokines (e.g. TNFalpha, IL-2), and bystander/abscopal effect
Also, compared to splenectomy, a marked and persistent cytopenias (which may lead to significant complications)
No firm RT schedules, but low dose (<=1Gy) intermittent (2-3 fx/week), to total <=10 Gy recommended. One report suggests conventional 2 Gy/fx may be equally well tolerated. Consider dosing as follows (PMID 11230883 below):
Lymphoproliferative: 4-10 Gy total in 1 Gy/fx
Myelofibrosis: 1-9 Gy total, with 0.25-0.5 Gy/fx
Hypersplenism: RT typically not useful, but for example see PMID 18301984
Patients should be continuously monitored, and fields adjusted with shrinking spleen
RT should be stopped when therapeutic goal is achieved, rather than when prescription is reached
Complications are primarily myelosuppression, and need to be monitored daily (CBC, exam)
Toxicity tolerable in lymphoid disorders, higher in myeloproliferative disorders
Decline in hemoglobin - can lead to MI
Thrombocytopenia - can result in significant bleeding
Retreatment as necessary, with consideration of renal dose
Retrospective. 49 patients (CLL 6, CML 14, NHL 6, MPD 16, OMF 6, AML 1) treated with 85 courses with A) low dose <1 Gy/fx prolonged vs. B) conventional 2Gy/fx. Spleen pretreatment doses 3-70 Gy (mean 21 Gy)
Outcomes: spleen reduction 55/85 patients (Group A 47/72, Group B 8/13), clinical improvement 62/85 (Group A 57/72, Group B 5/13). Rapid response in 23 patients, with field reduction during treatment
Conclusion: Conventional short treatment showed rapid response, no difference in toxicity
Naval Medical Center, San Diego, 2003 (1990-2001) PMID 12714892 -- "Palliative irradiation of the spleen." (McFarland JT, Am J Clin Oncol. 2003 Apr;26(2):178-83.)
Outcome: 22/25 treatments resulted in decreased pain and symptoms. 5 patients retreated, 1 patient 5 treatments
Conclusion: Effective palliation. Retreatment possible. Less effective for ITP or leukocytosis
Mayo, 1998PMID 9827926 -- "Splenic irradiation for symptomatic splenomegaly associated with myelofibrosis with myeloid metaplasia." (Elliott MA, Br J Haematol. 1998 Nov;103(2):505-11.)
Retrospective. 23 patients with MMM treated with 50 courses of SI. RT: Median total dose 2.8 Gy, given in median 7.5 fractions.
Outcomes: 94% reduction in spleen size. 8/23 received multiple courses, 9/23 underwent splenectomy
Toxicity: 43% significant cytopenia, 26% life-threatening cytopenia after a single course, 13% fatal sepsis or hemorrhage
Conclusion: Good symptomatic relief, but high risk. Should not be offered to good surgical candidates for splenectomy
Melbourne, 1989 (Australia) PMID 2912945 -- "A study of splenic irradiation in chronic lymphocytic leukemia." (Guiney MJ, Int J Radiat Oncol Biol Phys. 1989 Jan;16(1):225-9.)
Retrospective. 22 patients with 32 courses of SI. RT 0.25 - 0.5 Gy/fx, fields AP/PA and decreased with response, treatment halted with response
Toxicity: leucopenia, thrombocytopenia. No correlation with fraction size
1986 (1973-1982) PMID 2427184 -- "Splenic irradiation in the treatment of patients with chronic myelogenous leukemia or myelofibrosis with myeloid metaplasia. Results of daily and intermittent fractionation with and without concomitant hydroxyurea." (Wagner H, Cancer. 1986 Sep 15;58(6):1204-7.)
Retrospective. 17 patients with CML or MMM treated with 24 courses.
RT initially 1Gy to 15-20 Gy over 1 month, later 0.15-0.5 Gy/fx, total 0.15-6.5 Gy, given in 2-3 fx/week
Outcomes: 71% improvement for splenic pain, 50% improvement for splenomegaly
1977PMID 74374 -- "Irradiation for control of hypersplenism and painful splenomegaly in myeloid metaplasia." (Greenberger JS, Int J Radiat Oncol Biol Phys. 1977 Nov-Dec;2(11-12):1083-90.)
Cumulative total doses 5-10 Gy, well tolerated
No correlation between dose and spleen reduction and toxicity
Harvard; 2008PMID 19092156 -- "Case records of the Massachusetts General Hospital. Case 39-2008. A 51-year-old woman with splenomegaly and anemia." (Abramson JS, N Engl J Med. 2008 Dec 18;359(25):2707-18.)
Tubingen, 2001 (Germany) PMID 11230883 -- "Clinical indications and biological mechanisms of splenic irradiation in chronic leukaemias and myeloproliferative disorders." (Weinmann M, Radiother Oncol. 2001 Mar;58(3):235-46.)