Page 1834 - Williams Hematology ( PDFDrive )

1808 Part XI: Malignant Lymphoid Diseases Chapter 110: Heavy-Chain Disease 1809

ifosfamide, methotrexate, etoposide (VP-16), and dexamethasone. μ-HEAVY-CHAIN DISEASE DEFINITION
46
Surgical resection should be considered for focal or bulky transmural
lymphomatous tumors and extramedullary plasmacytoma. Autologous AND HISTORY
hematopoietic stem cell transplantation has been recommended for
34
patients with advanced or refractory disease, but to our knowledge μ-HCD is a proliferative disorder of B lymphocytes defined by the rec-
there are no reports in the literature demonstrating the usefulness of ognition of monoclonal deleted μ-HCs. In the first reported case, in
53
this approach. Previous trials have not incorporated immunotherapy 1969 by Forte and colleagues, the patient had chronic lymphocytic
with rituximab, an anti-CD20 monoclonal antibody, in the manage- leukemia. Since then, approximately 34 additional cases have been
54–57
ment of IPSID. As expected, the centrocyte-like cells are CD20-positive, reported.
but the plasma cells are not. In light of the extreme plasma cell differen-
tiation and the plasmacytic nature of large-cell IPSID lymphoma, there
is interest in investigating the value of treating patients with IPSID with EPIDEMIOLOGY
the novel agents (thalidomide, lenalidomide, bortezomib, pomalido- μ-HCD is extremely rare. In a series of 27 patients, the majority were
mide, or carfilzomib). white (76 percent) and male (55 percent). The median age at diagnosis
in 27 patients was 57.5 years (range: 15 to 80 years). 54

COURSE AND PROGNOSIS

The course of α-HCD is variable but generally progressive in the absence ETIOLOGY AND PATHOGENESIS
of therapy. Followup should include a periodic search for α-HCD pro- The cause of μ-HCD is unknown.
tein in serum and urine and, if negative, in the intestinal secretions.
Bowel radiography, ultrasonography, and esophagogastroduodenojeju-
nal endoscopy should be performed. A second-look laparotomy may CLINICAL FEATURES
be necessary. Relapses may occur after treatment at any stage of the
34
disease. The long-term prognosis for patients with α-HCD remains The most common presenting symptoms of patients with μ-HCD are
imprecise because of the lack of large series with prolonged followup. In those of a lymphoproliferative malignancy. An associated lymphoplas-
a small prospective Tunisian study, including eight patients with stage macytic proliferative disorder was noted in 22 of 27 patients at some
45
A disease and 15 with stages B and C, the survival of the total group time during the disease and designated as chronic lymphocytic leu-
54
was 90 percent at 2 years. A series from Turkey reported 5-year treat- kemia, lymphoma, Waldenström macroglobulinemia, or myeloma.
47
ment results of 23 patients with IPSID, including five with secretion of α μ-HCD protein has been described in one patient each with systemic
chains. In patients with stage A disease, tetracycline yielded a 71 percent lupus erythematosus, hepatic cirrhosis, hepatosplenomegaly with
54
complete response. The 5-year overall survival rate for the entire group ascites, pulmonary infection, splenomegaly with pancytopenia, and
55
was 70 percent. However, the median overall survival for 3 patients with myelodysplasia. Three cases of μ-HCD associated with amyloidosis
immunoblastic lymphoma was only 7 months. have been reported. 58
Thirteen patients were studied who had IPSID associated with Splenomegaly and hepatomegaly are common in μ-HCD and were
54
α-HCD. Six patients, two with high-grade lymphoma and four with noted in 21 of 22 and 15 of 21 patients, respectively. Peripheral lymph-
48
low-grade disease, received chemotherapy or radiotherapy or both. adenopathy was described in 10 of 25 patients. 54
One patient died at 76 months, and five were alive at an average of 92
months. Five patients with low-grade disease received conservative
therapy (antibiotics and in some cases prednisone). All five patients LABORATORY FEATURES
were alive at an average of 40 months after presentation. Three of these
five patients achieved remission at 5, 6, and 27 months. Two of the five MOLECULAR BIOLOGY AND GENETICS
patients had persistent disease at 20 and 25 months. Two patients did The molecular weight of the μ-HCD protein determined in eight
not receive treatment and died of high-grade lymphoma. patients ranged from 26,500 to 158,000. The higher molecular weights
Another study described six patients who had α-HCD with lym- are thought to be the result of polymerization of the μ-chain fragments.
49
phoma. All patients responded poorly to chemotherapy; the median The μ-HCD fragments from 6 patients were subjected to detailed chem-
duration of survival was 10.5 months. ical analysis. Figure 110–5 depicts the structure of these six μ-HCD pro-
A subsequent study described 12 patients with secretory and teins compared with that of normal μ-HC. The V domain is absent in
50
H
nonsecretory IPSID. Six patients presented with stage A disease. Four all cases. The normal sequence began with C 1 in three cases, C 2 in
H
H
patients responded to antibiotic or glucocorticoid therapy. In two two cases, and C 3 in one case. There are sequence data for only 1 gene
H
patients, stage A disease evolved into stage C. Three patients presented coding for a μ-HCD protein (Fig. 110–6).
with stage B disease. Two of these patients responded completely to che-
motherapy, and the third refused treatment and died after 16 months.
Three patients with stage C disease at diagnosis received aggressive SERUM AND URINE PROTEIN FINDINGS
combination chemotherapy and remained in complete remission with a A monoclonal spike was found on serum protein electrophoresis in less
median followup of 2.2 years. than half of a series of patients with μ-HCD (eight of 19). The diagnosis
54
Preliminary results suggest that flow cytometric analysis of S-phase of μ-HCD is made by documentation of the abnormal HC. Immunofix-
fraction and certain immunomarkers, such as syndecan, Bcl6, and ation of both serum and urine should be done. When these procedures
51
p53, may be useful prognostic indicators in the clinical management yield ambiguous results, two-dimensional gel electrophoresis is a use-
52
of patients with IPSID. Patients with a poor prognosis have a higher ful additional tool. The combination of capillary immunotyping elec-
fraction of cells in S phase, lower syndecan-1 expression, and higher trophoresis and high-resolution two-dimensional electrophoresis has
Bcl6 expression than those with a good prognosis. been used successfully for the detection of μ-HCD in one patient,
59

Kaushansky_chapter 110_p1803-1812.indd 1809 9/18/15 9:59 AM