Page 510 - Hematology_ Basic Principles and Practice ( PDFDrive )

430 Part IV Disorders of Hematopoietic Cell Development

Oral cyclophosphamide may be started at a dose of 50 mg PROGNOSIS
orally (PO) daily, with a maximal dose of no more than 150 mg
daily. Blood counts should be monitored, and the dose may be The prognosis of secondary PRCA depends upon the underlying
escalated accordingly. Trials of therapy longer than 3 months disease. Idiopathic PRCA may be very refractory to treatment. Ulti-
without signs of response are not warranted. Monitoring of the mately, remission may be achieved in a significant proportion
reticulocyte count may allow for the early assessment of response. (approximately 68%) of patients, especially when sequential regimens
Often, a delayed response may be seen when cyclophosphamide is are used. Spontaneous remissions are observed in 5% to 10% of cases.
withdrawn, reflective of balance between immunosuppression and Relapses are common, especially during the first year postremission
cytotoxicity. but are usually responsive to the same regimen that induced remis-
Rituximab given IV infusion weekly for 4 weeks has been found sion. Chronic, low-dose immunosuppressive therapy may be needed
to be efficacious in PRCA. PRCA in a variety of settings, including in certain cases that have relapsed. In one study, median survival was
B-cell CLL, EBV-associated posttransplant lymphoproliferative reported to be 14 years. Unlike a megakaryocytic thrombocytopenic
disease, ABO-incompatible allogeneic HSCT for acute myeloid purpura, evolution to aplastic anemia is rare and very few patients
leukemia, and hairy cell leukemia variant, has been successfully (3% to 5%) evolve into acute leukemia.
treated with Rituximab. In cases refractory to immunosuppressive
agents affecting T-cell function, rituximab or low-dose alemtuzumab
constitute a reasonable option. Rituximab is effective in patients with ACQUIRED WHITE BLOOD CELL
PRCA owing to ABO incompatibility following bone marrow PRODUCTION DISORDERS
transplantation.
CsA can be administered at a dose of 5–10 mg/kg PO daily in Neutropenia is a common condition. The majority of cases are sec-
divided doses. CsA can be combined with prednisone at doses of ondary to a variety of causes, including systemic or hematologic
20–30 mg PO. The trough levels of CsA should be monitored. An diseases. We will describe a primary, isolated form of neutropenia in
adequate trial of therapy is considered 3 months of therapy. The which other hematopoietic lineages are not affected. In such a setting,
response rates may be as high as 60% to 80%. After a response is neutropenia may be the result of peripheral destruction or perhaps
achieved, the therapy should be continued for 6 months followed by less frequently the result of the absence of myeloid progenitors in the
a slow taper. marrow. The cutoff value for the diagnosis of neutropenia is an
Horse ATG may be given to refractory cases at a dose of 40 mg/ absolute neutrophil count (ANC) of less than 1500 cells/µL. This
kg IV daily for 4 days with prednisone at 1 mg/kg. Concomitant value is generally accepted as a definition for neutropenia for all ages
prednisone should be administered and then tapered over 2–3 weeks. and ethnic backgrounds except for newborn infants. Clinically, the
A therapeutic response should occur within 3 months posttherapy, most concerning consequence of neutropenia is the propensity to
although responses at or beyond 6 months may be observed. develop infections. However, the correlation between ANC and the
Daclizumab, an anti–interleukin (IL)-2 receptor antibody propensity for infection is variable in different circumstances and
(Zenapax, anti-CD25 mAb), may constitute a good alternative to determined by marrow neutrophil reserves, duration of neutropenia,
ATG. A dose of 1 mg/kg of body weight IV is administered every 2 and clinical context. This is best illustrated in patients with chronic
weeks. While dacluzimab is not currently on the market other benign neutropenia of childhood and infancy, where patients may
anti–IL-2 are available options. have an ANC as low or less than 250 cells/µL and yet they may be
Methotrexate, an antimetabolite, at low doses (7.5–15 mg/week devoid of infections or only have mild infections.
PO) is useful in treating PRCA, especially in patients with concomi-
tant LGL leukemia. The responses are generally sustained, and
therapy is well tolerated. Methotrexate may be given in conjunction CLASSIFICATION OF ACQUIRED NEUTROPENIAS
with other therapies like CsA.
Alemtuzumab (Campath, anti-CD52 monoclonal antibody) is a Neutropenia as a primary disease should be distinguished from
recombinant DNA–derived humanized monoclonal antibody inherited forms of neutropenia, which commonly present during
directed against the cell surface glycoprotein CD52, which is expressed early childhood (see Chapter 29), and secondary forms of neutropenia
on the surface of normal and malignant B and T lymphocytes. Cur- associated with systemic disorders. In addition, idiopathic neutrope-
rently approved for multiple sclerosis and available on compassionate nia is distinct from the constitutional or familial benign neutropenia
use for other indication. Former IV dosing has been replaced with frequently seen in African Americans, Yemenites, and Falasha Jews or
SC (initial dose of 3 mg, and subsequent doses at 10 mg once or black Bedouins. The degree of neutropenia is often mild, and there
twice weekly). The usual cumulative dose before response is usually is no propensity to develop infections. Most cases of neutropenia are
around 50–100 mg. Alemtuzumab has been tested in a variety of secondary to a variety of disorders. Primary autoimmune neutropenia
lymphoproliferative disorders, including B-cell lymphomas and (AIN) and idiopathic neutropenia are less common. We will limit
T-LGL leukemia. Similarly, PRCA occurring in the context of these our description to isolated forms of neutropenia (Table 32.4).
conditions previously unresponsive to other therapies has been shown
to be responsive to this agent.
Primary Neutropenia
Hematopoietic Stem Cell Transplantation Most cases of neutropenia are secondary to various hematologic and
systemic diseases. However, in a small proportion of cases, an inciting
Despite advances in immunosuppressive regimens, subsets of patients cause cannot be identified despite intensive testing. Such idiopathic
with PRCA remain refractory and are very difficult to treat. As with cases are most likely immune mediated.
other bone marrow failure disorders with autoimmune pathogenesis
like aplastic anemia, HSCT is an important treatment option espe-
cially for refractory and relapsed PRCA cases. Matched sibling donor Chronic Idiopathic Neutropenia in Adults
allogeneic HSCT results in restoration of normal hematopoiesis in
patients with refractory PRCA. In another case, a patient with Chronic idiopathic neutropenia in adults compared with those in
relapsed PRCA underwent matched sibling donor allogeneic HSCT infancy and early childhood has less tendency toward spontaneous
combined with donor lymphocyte infusions resulting in full donor remission, although it does generally remain clinically benign. There
engraftment and subsequent return of normal hematopoiesis, sug- may be concomitant anemia or thrombocytopenia that may portend
gesting a graft-versus-autoimmunity effect as the likely mechanism a higher incidence of splenomegaly, infectious complications, and
for response. antineutrophil antibodies (ANAs) that are complement fixing. A