Low dose cytarabine and
granulocyte/macrophage-colony stimulating factor induced long-term
remission in a patient with acute myeloid leukemia in early
relapse after intensive chemotherapy
José Luis Sastre, Carlos Ulibarrena, Isabel
Cantón, Marina Iglesias, Socorro García-Torremocha,
María Obdulia Vázquez
Servicio de Hematología., Cristal Piñor Hospitais,
Ourense. Spain.
Correspondence: José Luis Sastre, Servicio de
Hematología., Cristal Piñor Hospitais, Ourense,
Spain. Phone: international +34-88-385629 or 34-88-385835 . Fax:
international +34-88-385551. E-mail: jlsastre@cristalp.es
In April 1997, a 61-year-old was diagnosed of AML-M1 with an
abnormal 45, XY,-18 karyotype (10 metaphases) and trilineal
dysplasia in bone marrow aspirate (BM) . A first complete
remission (CR) was achieved with the classic daunoblastin +
cytarabine regimen. A course of consolidation was then delivered
without complications. After a third cicle consisting of
mitoxantrone, cytarabine and etoposide, the patient presented with
a persistent febrile pancytopenia and a growing number of
myeloblasts in BM and peripheral blood smears. He refused
additional courses of intensive chemotherapy. For this reason,
after informed consent, he commenced monthly courses of low dose
cytarabine (LD araC) (10 mg/m2/day, days 1-14) and
granulocyte/macrophage-Colony Stimulating Factor (GM-CSF) (150
mg/day, days 1-14), in August 1997. In March 1998, after the sixth
cycle, 13% of myeloblast remained in bone marrow aspirate. In
October 1998, only 2% of residual blasts persisted and the
cytogenetic study showed the coexistence of two clones: 46,XY and
45, XY, -18 in 24 and 4 metaphases respectively. Recently, in
August 2000, after 36 courses, trilineal dysplasia was still
present but all metaphases were normal, and only 2% myeloblasts
(less than 2% CD34 or CD117 positive cells by flow cytometry) were
detected in BM. Side effects were mild and non-limiting: flu-like
syndrome, dysgeusia and hyporexia related to GM-CSF
administration. The patient remains stable without complications
40 months after the onset of this protocol. The whole treatment
was administered at home by her daugther; both drugs being provide
by the Hospital Pharmacy. The patient follow-up was ambulatory
since September 1997 and he did not need more transfusions. In AML
patients early relapses reflect drug resistance and are unlikely
to be rescued by salvage chemotherapy. The chance of cure by bone
marrow transplantation is handicapped by age itself, since it is
not a feasible procedure over 60. Blood transfusions and
palliative measures are the commonest approach in relapses, for
many weeks or months, until death. In this paper, we propose an
alteranative with reduced-dose therapy on an outpatient basis.
Combined therapy with LD araC and GM-CSF yield responses of short
duration in elderly patients with MDS and AML.1,2
Initially it was thought that araC induced differentiation of
immature myeloid cells; whereas recent avalaible data suggest that
its main effect lies on its cytotoxicity.3 GM-CSF
stimulates non clonal hematopoiesis and suppresses the neoplastic
clone.4 The benefit of both drugs administered togheter
has been investigated in the last two decades;5; its
rationale being the ability of growth factors to recruit more
progenitors into the cell cycle, thus making them more susceptible
to ara-C.6,7 The improvement in older's patients'
outcome with this therapy has not been proven.1,5
Fortunately, in our case, myeloblasts decreased, the abnormal
clone disappeared, peripheral blood counts became normal and he
regained a normal performance status, facts that can not be
attributable to chance. Up till now, most reports analyze their
results after few courses of this scheme;1 on the
contrary , this patient received multiple cycles. It is possible
that this strategy, as we applied in high risk MDS patients, could
allow for this progressive and sustained response.2,8
In view of this individual case, we believe that this relatively innocuous scheme could deserve application in others elderly patients at diagnosis or in relapse after intensive chemotherapy.
