Page 2500 - Hematology_ Basic Principles and Practice ( PDFDrive )

2232 Part XIII Consultative Hematology

predominantly case reports in the pediatric literature, in one review
Treatment of Immune-Mediated Thrombocytopenia After Solid Organ
Transplant in Children of neutropenia after 400 renal transplants in adults, 35 cases (9%)
365
were reported. The etiology of leukopenia or neutropenia is similar
There is no standard approach to the treatment of immune-mediated in children and adults and includes immunosuppressive agents; other
thrombocytopenia that occurs after solid organ transplant. First, all myelosuppressive drugs (e.g., ganciclovir); infection (e.g., CMV,
other causes of thrombocytopenia should be ruled out before beginning sepsis); and, less frequently, INF, PTLD, hypersplenism, and idio-
therapy for what is often a presumptive diagnosis of immune-mediated pathic. Use of TAC is often implicated as a possible contributing
thrombocytopenia. If the thrombocytopenia is mild to moderate factor.
(>20,000 to 30,000/µL) with no associated bleeding symptoms, we Both filgrastim (granulocyte colony-stimulating factor) and sar-
usually observe without intervention and monitor the platelet count gramostim (granulocyte macrophage colony-stimulating factor) have
on at least a weekly basis. If the platelet count is less than 10,000 to been used to treat neutropenia in adults and children. In adults, it
15,000/µL or if there is bleeding, immediate treatment is initiated with
high-dose corticosteroids: 4 mg/kg/day of prednisone (or intravenous has resulted in improvement of the WBC count in more than 90%
365,366
equivalent) divided into three or four doses and continued for 4 days. If of patients after three or four doses. There was no evidence of
there is a response (i.e., platelet count >20,000/µL), the corticosteroid precipitation of rejection. In the case reports of children, both agents
is dropped to 2 mg/kg/day divided into two or three doses and then have been found to be effective in most patients, but there is a sug-
slowly tapered to zero over the subsequent 2 to 3 weeks. Intravenous gestion that efficacy may be affected by continuation of TAC. 364,367,368
immunoglobulin or anti-RhD in standard doses for childhood idiopathic Although cytokine therapy has been shown to increase the neutrophil
thrombocytopenic purpura can be used if there is no response to count, there is insufficient data to prove the effectiveness of prevent-
high-dose corticosteroids. ing or treating infection or decreasing mortality. 369
For patients who have recurrent or chronic thrombocytopenia There has been one report on the use of granulocyte transfusions
requiring multiple courses of treatment to maintain platelet counts
greater than 10,000 to 15,000/µL, we have used vincristine (1.5 mg/ in solid organ transplant recipients, including one child. Of the 14
2
m [maximum dose, 2 mg] intravenously weekly for 6 weeks) with patients studied, 11 showed an increase in ANC greater than 1000/µL
success. Rituximab (375 mg/m intravenously weekly for 4 weeks) by the end of the course. Of 12 patients with infections, 4 (33%)
2
has infrequently been used in this situation. For patients taking showed a clinical response. Additional studies are needed to evaluate
tacrolimus with refractory thrombocytopenia, serious consideration the efficacy of granulocyte transfusions in transplant patients. 369
should be given to switching to an alternative immunosuppressant Azathioprine is well known to cause myelosuppression and has
drug because this may be necessary for resolution of the throm- been associated with moderate to severe neutropenia. Azathioprine is
bocytopenia. Involvement of both the transplant team and the catabolized in vivo by xanthine oxidase and thiopurine methyltrans-
hematology team is necessary for ideal management of these complex ferase (TPMT). TPMT activity can vary considerably depending on
patients.
a genetic polymorphism. Approximately 0.3% of white persons are
homozygous and 11% are heterozygous for deficiency of TPMT.
Severe myelosuppression, including fatal neutropenia, has been docu-
mented in transplant patients who are homozygous for TMPT
370
and one patient’s thrombocytopenia resolved after an episode of deficiency and receiving azathioprine. Some data suggest that
severe graft rejection (see box on Treatment of Immune-Mediated monitoring 6-thioguanine nucleotides (the metabolites of azathio-
Thrombocytopenia After Solid Organ Transplant in Children). prine) may allow for individualized management of azathioprine
dosing with fewer side effects, although this has not become common
371,372
Infection-Associated Thrombocytopenia practice.
Neutropenia has also been associated with the use of MMF and
Posttransplant sirolimus. Neutropenia and thrombocytopenia have been noted as
373
side effects of MMF since 1998. Leukopenia may affect 5% to 11%
Although there are few published reports, one would expect the same of patients taking the drug, and pseudo Pelger-Huet anomaly has also
hematologic problems, including thrombocytopenia, associated with been noted. 374,375 The leukopenia is often seen within 2 to 8 months
bacterial sepsis or other serious infections as seen in nontransplant after starting the drug. Filgrastim has been effective in reversing the
patients. Infection with HHV-6 and the herpesvirus group has been neutropenia, although some patients require decreasing the dose or
studied closely. HHV-6 is commonly seen after transplant, mostly in stopping the drug. Ganciclovir and valacyclovir are commonly used
stem cell transplant recipients. In adults after liver transplant, there simultaneously with MMF to treat or prevent CMV disease. These
376
are case reports of a syndrome of HHV-6 infection with thrombocy- drugs are also known to be associated with neutropenia. There may
359
topenia, fever, and encephalopathy. This syndrome has not been be an interaction between these drugs that increases the risk for
reported in children with HHV-6 infection. 360,361 neutropenia. 377,378 It may be necessary to stop ganciclovir as well as
374
Herpesvirus infection after kidney transplant in children is seen MMF for the neutropenia to improve. Of note, serious infections
in about one-third of patients, with CMV being the most common are infrequently encountered.
362
infection. The hematologic abnormalities associated with herpes- In two reports of the use of sirolimus in children, neutropenia was
virus infection include thrombocytopenia and leukopenia, with the most common toxicity, along with hepatitis, hyperlipidemia, and
incidence rates of 31% and 24%, respectively. These and other mouth ulcers. 379,380 It is not clear whether the neutropenia is directly
symptoms of herpesvirus infection occur at the same frequency as in related to serum level of the drug. Most counts improve with a
nontransplant patients. There is a case report of a child after liver decrease in the drug dose, although a few patients need to have the
transplant who developed measles complicated by autoimmune drug discontinued.
thrombocytopenia and neutropenia. 363
Pancytopenia
White Blood Cells
Pancytopenia is seen in two settings after solid organ transplant. The
Leukopenia and neutropenia after solid organ transplant are uncom- first is early after liver transplant for acute liver failure from acute
monly reported in the literature, although this may not reflect the infectious hepatitis. 381,382 This represents the known aplastic anemia
364
true incidence seen in practice. Authors of two reviews of hemato- that can be seen in as many as one-third of patients after non–A-E
logic complications in children after transplant reported isolated hepatitis. Treatment and outcome are similar to those in patients with
neutropenia in 2 (3%) of 70 patients after liver transplant and 9 (8%) posthepatitic aplastic anemia who do not require liver transplant. The
of 106 patients after cardiothoracic transplant. 312,313 Neutropenia was second setting is delayed pancytopenia, which may be secondary to
331
383
also seen in combination with other cytopenias. Although there are infection with or without PTLD. A number of cases have been