Haematologica
2000; 85:E03
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Thrombotic thrombocytopenic
purpura treatment: a point of view
Gerlando Quintini, Vincenzo Barbera, Maria Dieli, Emilio
Iannitto, Guglielmo Mariani
Division of Hematology and Bone Marrow Transplantation,
University of Palermo, Italy
Correspondence: Gerlando Quintini, M.D., Divisione di Ematologia
con Trapianto, Università degli Studi di Palermo, via del
Vespro 129, 90127 Palermo, Italy. Phone: international
+39.091.6554314. Fax +39.091.6554402, E-mail gequint@tin.it
Abstract
Rock and co-workers recently
reported in their paper entitled Thrombotic thrombocytopenic
purpura treatment in year 2000 that plasma exchange may be
considered the only therapy of proven efficacy. In addition,
several studies on the pathogenesis of TTP suggest the use of
steroids. However, a considerable number of patients relapse and a
proportion of patients do not respond to these measures. A gold
standard for treatment has still not been defined in this setting
and the prognosis is poor. We reported the case of a young man
with acute resistant TTP successfully treated with autologous stem
cells transplant after conditioning with cyclophosphamide, anti-T
lymphocyte globulin and prednisone. This case supports the
therapeutic value of aggressive immunosuppression for the
management of resistant TTP.
Text
We read with interest the recent
paper by Rock et al. (Haematologica
2000; 85:410-419)
entitled Thrombotic thrombocytoenic purpura treatment in year
2000.1 The authors stated that plasma exchange
remains the treatment of choice for thrombotic thrombocytoenic
purpura (TTP). There is indeed evidence that patients with TTP
have abnormalities in their plasma that may be corrected by plasma
infusion or plasma exchange (PE). Furlan2 and
Tsai3 reported a reduction or absence of a
metal-containing proteolytic enzyme (metalloprotease) involved in
the cleavage of large von Willebrand factor (vWF) multimers to
smaller size molecules. Thus, TTP might result from a deficiency
of metalloprotease, which gives rise to an increase of unusually
large vWF multimers inducing platelet aggregation. Moreover, IgG
autoantibodies against metalloprotease have been detected in
patients with acute TTP. These observations clearly explain the
dramatic improvement of the outcome of TTP due to introduction of
PE, which removes both large vWF multimers and autoantibodies,
and, at the same time, provides new molecules of metalloprotease
from normal donors. To-date PE can give remissions in about 80% of
patients and may be considered the only therapy of proven
efficacy.4 Unfortunately, PE is not always successful
and approximately 10% of patients may succumb to TTP. Thus,
alternative strategies are necessary to successfully treat those
cases that do not respond to PE. Several treatment options have
been suggested for PE-resistant patients, but most of them are
based on anecdotal reports or on the study of small cohorts.
Nonetheless we would like to call attention to the case of a
20-year-old man whose disease remitted with high dose
cyclophosphamide followed by autologous stem cell transplantation
(ASCT), as we recently reported.5 The patient had been
previously treated with PE and steroids daily, and then with
weekly pulses of vincristine and intravenous immunoglobulin.
However, his TTP failed to respond to treatment and we decided to
treat the patients with aggressive immunosuppression and ASCT,
since high dose cyclophosphamide and ASCT produce profound
immunosuppressive and immunomodulatory effects that may have
clinical relevance for the treatment of severe autoimmune
disorders.6 Peripheral blood progenitor cells were
mobilized with cyclophosphamide (4 g/m2) plus G-CSF.
Conditioning regimen included cyclophosphamide, anti-T globulin
and 6-methylprednisolone. Since receiving ASCT the patient has
maintained complete remission for more than two years. In another
report, a patient with recurrent TTP was successfully treated with
an intensified immunosuppressive regimen consisting of
cyclophosphamide, adryamicin, vincristine and prednisone
(CHOP).7 The case we have described supports the
concept of an autoimmune hypotesis for the pathogenesis of TTP and
indicate the necessity of alternative treatment modalities in the
management of refractory TTP. We would like to call attention on
the necessity to promote further studies to clarify the role of
this treatment in patients with particularly severe
disease.
