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1330 Part X: Malignant Myeloid Diseases Chapter 86: Primary Myelofibrosis 1331

prior to the availability of mutant tyrosine kinase (BCR-ABL) inhibi- SPLENECTOMY
tors (Chap. 89). Interferon-α has not been used extensively in primary Splenectomy has been important in the management of primary mye-
myelofibrosis, but has been useful for treatment of splenic enlargement, lofibrosis. The major indications for splenectomy include (1) pain-
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bone pain, and thrombocytosis in select patients. Trials comparing ful enlarged spleen (~50 percent of patients), (2) excessive transfusion
interferon therapy with hydroxyurea or other therapy have not been requirements or refractory hemolytic anemia (~25 percent of patients),
447
reported. Hydroxyurea is easier to use (oral versus parenteral) and (3) portal hypertension (~15 percent of patients), and (4) severe throm-
has less-frequent and less-severe side effects than interferon, especially bocytopenia (~10 percent of patients).
in older patients. A polyethylene glycol conjugated interferon-α prepa- Patients who have a prolonged bleeding time or coagulation times
ration may prove more practical and tolerable for use in patients with are at serious risk for hemorrhage with surgery and should not undergo
myelofibrosis. Although largely ineffective in later stages of myelofibro- the procedure unless the abnormalities can be corrected by platelet
sis, it has shown efficacy in the early myeloproliferative stage of primary transfusion and factor replacement therapy. Evidence of low-grade
myelofibrosis with mild to moderate marrow fibrosis. 448–451
intravascular coagulation, such as elevated D-dimer levels, may require
prophylactic heparin therapy and platelet transfusion should excessive
Serosal Implants bleeding occur.
Cytarabine Ascites resulting from peritoneal hematopoietic implants Removal of the spleen in patients with primary myelofibrosis may
452
has been treated with intraperitoneal cytarabine. Intrasplenic cytara- be difficult. Usually the spleen is adherent to neighboring serosal sur-
bine administered via a splenic artery catheter has resulted in significant faces and structures (e.g., inferior surface of left hemidiaphragm) and
improvement in a patient (see also “Radiotherapy” below). 453
has numerous collateral vessels and very dilated splenoportal arteries
and veins. Immediate postoperative mortality is a function of surgical
IMMUNE-RELATED FIBROSIS experience and skill and of the rapidity of recognition of postoperative
Intravenous Immunoglobulin complications. In experienced hands, perioperative mortality is approx-
imately 10 percent. Postoperative morbidity from hemorrhage, sub-
Although autoimmune or systemic lupus erythematosus-related mye- phrenic hematoma, subphrenic abscess, injury to the tail of the pancreas,
lofibrosis has responded to glucocorticoids or intravenous immune pancreatic fistulas, or portal vein stump or mesenteric vessel throm-
globulin 251,254 and a variety of other fibrotic disorders occasionally bosis occurs in approximately 30 percent of patients. Infection, espe-
respond, primary myelofibrosis does not have a sustained response cially, pneumonia occurs in approximately 10 percent of patients. Later
454
to such therapy because the fundamental lesion is the hematopoietic postoperative changes include liver enlargement (sometimes massive),
multipotential cell neoplasm, neoplastic megakaryocytosis, severe extramedullary hematopoietic tumors, thrombocytosis, and a decrease
megakaryocytic dysmorphia, and cytokine release with resultant fibro- in teardrop-shaped red cells. Leukemic blast transformation occurs in
genesis and, sometimes, osteogenesis. approximately 15 percent of patients after splenectomy. Hydroxyurea
or aspirin and anagrelide may be useful for exaggerated thrombocyto-
BISPHOSPHONATES FOR BONE DISEASE sis (Chap. 85). The morbidity and mortality from splenectomy and the
Debilitating bone pain can be a vexing problem in some patients with modest extension of life have led to increasing conservatism regarding
its use. However, splenectomy can improve the condition for which it
osteosclerosis and periostitis. Dramatic improvement in bone pain and was performed in approximately 50 percent of patients. Median survival
hematopoiesis after etidronate 6 mg/kg per day on alternate months after splenectomy has been approximately 18 months.
455
or clodronate 30 mg/kg per day for several months, during which
marked improvement was still present 33 months later, highlight the
456
potential usefulness of this family of drugs for bone symptoms. 457 PORTAL-SYSTEMIC VASCULAR SHUNT
SURGERY
RADIOTHERAPY Circulatory dynamic studies are performed at the time of surgery in
patients undergoing operation for portal hypertension and bleeding
Radiotherapy can be useful for patients with primary myelofibrosis in varices or refractory ascites. In patients in whom the hepatic wedge
several situations. For example, in the presence of severe splenic pain pressure elevations result from markedly increased blood flow from
(splenic infarctions) or massive splenic enlargement with contraindi- the spleen to the liver, the preferred treatment procedure for portal
cation to splenectomy (e.g., thrombocytosis), repeated doses of 0.5 to hypertension is splenectomy. In patients who have portal hypertension
2.0 Gy to the spleen can ameliorate the pain. Splenic radiation can resulting from intrahepatic block or hepatic vein thrombosis and who
458
result in further cytopenias or worsening cytopenias, especially throm- have a hepatic venous pressure gradient well above the upper limits of
bocytopenia, referred to as an abscopal effect on marrow production, normal (6 torr), a splenorenal shunt can be performed or, to avoid
463
perhaps because of the circulation of large numbers of CD34+ cells abdominal surgery, a transjugular intrahepatic portosystemic shunt can
exposed in the spleen. Other situations in which radiation may be use- be used. 464,465 Variceal sclerotherapy or variceal ligation has been used to
459
ful are ascites resulting from myeloid metaplasia of the peritoneum, treat bleeding varices resulting from portal hypertension.
focal areas of severe bone pain (periostitis or the osteolysis of a myeloid
sarcoma), 272,458,460 and extramedullary fibrohematopoietic tumors, 157,458 HEMATOPOIETIC STEM CELL
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especially of the epidural space. Low-dose radiation to the liver
for symptomatic hepatomegaly and ascites provides only short-term TRANSPLANTATION
relief. 458,461 Low-dose radiotherapy to the lung has been used success- Marrow transplantation is the only curative approach to primary mye-
fully to palliate the effects of pulmonary hypertension thought to result lofibrosis. Marrow transplantation therapy has been used increasingly
from extensive extramedullary hematopoiesis in the organ. Low-dose in younger patients with a poor prognosis (e.g., severe anemia and
radiotherapy has relieved signs of respiratory insufficiency, especially leukopenia or exaggerated leukocytosis) who have a histocompatible
hypoxemia, but in several unreported instances known to the authors, sibling. 466–473 The median age in most studies is approximately 50 years,
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this approach has led to deterioration of pulmonary function. whereas the median age of all patients is approximately 70 years.
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