Molecular And Cytogenetic Remission In A Case Of Subtype M4e Acute Myelogenous Leukemia With Minimal Monthsochemotherapy: High Sensitivity Or Spontaneous Remission?
MARTelli, M. P., Latagliata, R., Spadea, A., Avvisati, G., Mancini, M., Romano, A., Luzi, G., & Petti, M. C. (2000). Molecular and cytogenetic remission in a case of subtype M4E acute myelogenous leukemia with minimal monthsochemotherapy: high sensitivity or spontaneous remission?. European journal of haematology, 65(3), 203–206. https://doi.org/10.1034/j.1600-0609.2000.9c220.x
View Original Source →Abstract
Complete remission was observed in an adult patient with acute myelogenous leukemia after minimal monochemotherapy. Remission occurred after a severe febrile pneumonia and was accompanied by cytogenetic and molecular remission. The hypothesis of spontaneous remission was raised, even if a high sensitivity to low-dose cytostatics cannot be excluded. Such spontaneous complete remissions, often associated with bacterial infections and blood transfusions, are extremely rare, and are usually of short duration. Previous cases are summarized, and the role of etiologic factors is discussed.
Case Details
Disease Location
Bone marrow
Personal Characteristics
26 -year-old female
Clinical Characteristics
Admitted in september 194 because of severe dyspnea, fever, and hyperleukocytosis, her WHO performance was a 4 physical revealed mild hepatomegaly chest x-ray and CT showed a pattern of diffuse reticulonodular markings, prominent in the lower areas of the lungs, small pleural effusions and subsegmental atelectasis in the lower right lobe arterial blood gas and ph values were ph 7.49, p(co2) 28.9mmhg, p(o2) 43.2mmhg, and o2(sat) 83.7%. Leukocyte count was 66.5x10^9/l with 5% polymorphonuclears and 91% circulating monocytoid-appearing blast cells hgb was 11.4g/dl, platelets were 23x10^9/l. Marrow aspirate was hypercellular with 70% blasts cells with basophilic cytoplasm, some with azurophilic granules and most of monocytoid appearance abnormal eosinophils with basophilic granules were also seen cells were positive for myeloperoxidase, nonspecific esterases and alpha-naphthyl-asd-chloroacetate esterase diagnosis of acute myeloid leukemia of the m4eo subtype was made immunphenotypic study showed positives for CD33, 13, HLA-dr and CD7. Cell kinetic study showed the presence of a hyperdiploid clone and cytogenetic analysis of g-banded chromosomes revealed 15/15 metaphases the following karyotype 46,xx,inv(16)(p13q22) right-pcr revealed cbfv/myh11 hybrid gene owing to interstitial pneumonia, chemo was delayed but supportive treatment including fluids, oxygen, antibiotics, corticosteroids and hydroxyurea for hyperleukocytosis during the first 2 weeks of hospitalization, 9 units of packed red cells were given, thrombocytopenia required 35 units of platelet transfusions in which a refractory state quickly occurred, 42 units of plasma were also given for coagulation abnormalities 25 months after the complete remission, hematological relapse occurred and cytogenetics revealed in 10/12 metaphases the karyotype 47,xx,+9,inv(16)(p13q22) molecular analysis showed the same alteration present at diagnosis the patient received reinduciton treatment with mitoxantrone, etoposide, and ara-c after a 4 day consolidation course with mec, an autologous marrow transplant was performed 19 days after the transplant the patient died from ileotyphlitis
Remission Characteristics
After 20 days, hematologic status improved significantly and marrow aspiration marked complete remission, 30 days after diagnosis marrow was normocellular with less that 5% blasts despite megakaryocyte dysplasia, there were no other abnormalities, peripheral blood was normal repeated cell kinetics showed the absence of hyperdiploid clone and cytogenetic analysis showed the karyotype normal in 20/20 metaphases repeat right-pcr revealed absence of cbfb/myh11 rearrangement one months later, hematological, cytogenetci and molecular remission was confirmed by a second marrow exam in which the patient was then treated with first cycle idarubicin, etoposide, and cytosine-arabinoside (ara-c); second cycle of mitoxantrone and intermediate doses of ara-c followed by 4 cycles of high doses of ara-c after relapse and subsequent reinduction treatment, a second complete remission was achieved
Treatment & Mechanisms
Proposed Remission Mechanisms
The systemic infection mounted host immune or humoral responses capable of leading the leukemic process to a sr also differentiating facts such as growth factors could be released during the infection (pneumonia) hydroxyurea may have contributed to cr sr may be linked to disappearance of genetic markers
Clinical Treatment
Fluids, oxygen, antibiotics (IV erythromycin for 9 days and IV trimethoprimsulfamethoxazole for 28 days), and corticosteroids ( prednisone) hydroxyurea transfusions first cycle idarubicin, etoposide, and cytosine-arabinoside (ara-c); second cycle of mitoxantrone and intermediate doses of ara-c followed by 4 cycles of high doses of ara-c reinduction treatment with mitoxantrone, etoposide, and ara-c autologous bone marrow transplant
Non-Clinical Treatment
None reported