Persistent bone marrow aplasia after intensive chemotherapy is uncommon, but is one of the fatal complications in patients with acute myeloid leukemia (AML). Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be contraindicated for patients who have hematologic diseases with serious infections, such as bacterial septicemia or invasive fungal diseases, combined with prolonged neutropenia due to frequent morbidity and mortality, such risks can be overcome by non-myeloablative conditioning and best supportive care. Here, we report an AML patient with persistent marrow aplasia after induction therapy, treated successfully with reduced-intensity allogeneic HSCT despite severe bacterial and fungal infections.
Anemia, Aplastic ; Bone Marrow* ; Drug Therapy* ; Hematologic Diseases ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute* ; Mortality ; Neutropenia ; Sepsis ; Stem Cell Transplantation* ; Stem Cells*

OBJECTIVETo evaluate the clinical characteristics and risk factors of clonal evolution after immunosuppressive therapy (IST) in children with severe/very severe aplastic anemia (SAA/VSAA).

METHODSThe clinical data of 231 children with newly-diagnosed SAA/VSAA who received IST were retrospectively studied. The incidence and risk factors of clonal evolution after IST were analyzed.

RESULTSThe 5-year overall survival rate of the 231 patients was 82.7%. Except for 18 cases of early deaths, 213 patients were evaluated for IST efficacy. Among the 231 patients, cytogenetic abnormalities for at least two chromosome metaphase were detectable in 14 (7.4%) patients, and PNH clones were detectable in either peripheral red blood cells or neutrophils for 95 patients. Among the 213 patients evaluated for IST efficacy, 15 patients experienced clonal evolution after IST. Five patients had PNH and trisomy 8 which were defined as favorable progressions, and ten patients experienced monosomy 7 and MDS/AML as unfavorable progressions. The 5-year accumulative incidence of favorable and unfavorable progression were (2.2±2.2)% and (4.8±3.3)%, respectively. Until the last follow-up, 100% (5/5) of patients with favorable progressions and 50% (5/10) of patients with unfavorable progressions survived. WBC>3.5×10/L, CD3T cell percentage>80%, dosage of antithymocyte globulin >3.0 mg/(kg·d) and no response to IST were related to unfavorable progressions by univariate analysis. Cox multivariate analysis revealed that an increased CD3T cell percentage (>80%) and no response to IST were independent risk factors for unfavorable progressions.

CONCLUSIONSThe children with SAA/VSAA who have an increased CD3T cell percentage at diagnosis or have no response to IST are in high risks of unfavorable progressions.

Adolescent ; Anemia, Aplastic ; drug therapy ; genetics ; immunology ; mortality ; Child ; Child, Preschool ; Chromosome Aberrations ; Clonal Evolution ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Infant ; Male ; Proportional Hazards Models ; Retrospective Studies

Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA.
Anemia, Aplastic/blood/diagnosis/mortality/*therapy ; Humans ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Iron Chelating Agents/adverse effects/*therapeutic use ; Risk Factors ; *Stem Cell Transplantation/adverse effects/mortality ; Survival Analysis ; Time Factors ; Treatment Outcome

The present study represents an analysis of 96 patients with severe aplastic anemia (SAA) treated in Seoul National University Hospital, Seoul, Korea between 1990 and 1999. Twenty-two patients were treated by allogeneic bone marrow transplantation (BMT) from HLA identical sibling donors and 74 by immunosuppressive therapy (IS) with antithymocyte globulin (ATG) or antilymphocyte globulin (ALG). There was no statistical difference between the two treatment groups in age, sex, disease duration, and previous transfusion amount. In the BMT group, grade II-IV acute graft versus host disease (GVHD) develeped in 10% and chronic GVHD occurred in 33% of patient. Only one patient died from complication of transplantation (veno-occlusive disease). Of 74 patients who received IS treatment, 45% achieved a complete or partial response. Twenty patients died among IS treatment group. Major causes of death were hemorrhage (40%) and infection (55%). In the BMT group, the 5-yr overall survival (OS) was 95% after a median follow-up of 42 months. In the IS group, the 5-yr OS was 70% after a median follow-up of 49 months (p=0.04). In conclusion, the long-term survival rates of SAA in Koreans receiving BMT or IS were excellent compared with the Western data. Further evaluation on the prognosis of aplastic anemia in Asians should be done.
Adolescent ; Adult ; Aged ; Anemia, Aplastic/mortality/*therapy ; Antilymphocyte Serum/*administration & dosage ; *Bone Marrow Transplantation ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Graft vs Host Disease ; Human ; Immunosuppressive Agents/*administration & dosage ; Male ; Middle Aged ; Neutrophils/cytology ; Severity of Illness Index ; Survival Analysis

BACKGROUND: Infections are still a frequent cause of morbidity and mortality in patients with hematologic malignancies. Antimicrobial prophylaxis in neutropenic patients has been practised for several decades. But, recently the rates of occurrence for pathogens have significantly changed (from predominance of gram-negative to gram-positive species) under selective pressure of antimicrobial prophylaxis, and novel resistance mechanisms have emerged. We investigated this study to assess the effectiveness of selective bowel decontamination for preventing infections in granulocytopenic patients who are receiving chemotherapy for acute myelogenous leukemia. METHODS: In a prospective, randomized trial, we evaluated the efficacy of oral ciprofloxacin (250 mg p.o. twice a day), roxithromycin (150 mg p.o. twice a day), fluconazole (50 mg p.o.) in 95 adult patients with acute myelogenous leukemia who undergone intensive chemotherapy. Prophylaxis was begun within 72 hours of initiation of the chemotherapy and continued until the onset of fever, signs or symptoms of infection, serious adverse effect, or recovery of the leukocyte count to > or = 1,000/mm3. RESULTS: 46 decontamination regimen treated patients and 49 control patients were assessable for efficacy. No difference was noted between the two groups in occurrence of fever during neutropenia, time to onset of first fever, sites of infection, duration of using systemic antimicrobials, overall infection rates, infection-related mortality, or hospitalization day. Decontamination regimen reduced the gram-negative infections, but increased the gram-positive infections. Among those who received decontamination regimen, the incidence of resistance to ciprofloxacin was 100% for gram-negative species. And resistance to erythromycin for gram-positive species, irrespective of decontamination, was very much high (90-100%). CONCLUSION: The approach of selective decontamination has not led to fewer febrile episodes or to a lower mortality in neutropenia after chemotherapy for acute myelogenous leukemia. It should be considered that we had better not prescribe decontamination regimen because of increment of infection due to gram-positive species and high resistance rate to fluoroquinolone and macrolide. Additional trials are needed to establish the efficacy of decontamination for other malignancies, aplastic anemia, or bone marrow transplantation.
Adult ; Anemia, Aplastic ; Bone Marrow Transplantation ; Ciprofloxacin ; Decontamination* ; Drug Therapy ; Erythromycin ; Fever ; Fluconazole ; Hematologic Neoplasms ; Hospitalization ; Humans ; Incidence ; Leukemia ; Leukemia, Myeloid, Acute* ; Leukocyte Count ; Mortality ; Neutropenia ; Prospective Studies* ; Roxithromycin

Adult ; Anemia, Aplastic ; mortality ; therapy ; Bone Marrow Transplantation ; Female ; Graft vs Host Disease ; etiology ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoietic Stem Cell Mobilization ; Humans ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Transplantation, Homologous

Anemia, Aplastic ; mortality ; pathology ; therapy ; Child ; Disease-Free Survival ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Immunosuppressive Agents ; therapeutic use ; Risk Factors ; Severity of Illness Index ; Tissue Donors ; Transplantation Conditioning ; methods ; Transplantation, Homologous ; Unrelated Donors

OBJECTIVETo compare the efficacy and safety of four different regimens for pediatric severe aplastic anemia (SAA) with immuno-suppressive therapy (IST) with or without combined human granulocyte colony-stimulating factor (G-CSF).

METHODThe authors retrospectively analyzed 105 children with SAA treated with IST with or without G-CSF in the hospital from February 2000 to September 2010. Regimen A, without G-CSF in the whole treatment, was used to treat Group A patients, n = 27; Regimen B, G-CSF, was initiated in Group B, n = 24, before the IST until hematologic recovery; Regimen C, G-CSF, was used together with the IST for Group C patients, n = 24, until hematologic recovery; Regimen D,G-CSF was used for Group D, n = 30, after the end of IST until hematologic recovery. The response rate, relapse rate, mortality, infection rate, infection-related death rate, risk of evolving into MDS/AML, survival rate, factors affecting the time of event-free survival and so on.

RESULT(1) The response (CR+PR) rates 4, 6, 12 and 24 months after IST of the whole series of 105 SAA children were 50.5% (7.6%+42.9%) , 60.0% (21.9%+38.1%) , 67.6% (38.1%+29.5%) and 69.5% (40.0%+29.5%) respectively. The 2-year survival rate was 90.5%; the follow-up of the patients for 13 years showed that the whole survival rate was 87.6%. (2) The differences of the response rates 4, 6, 12 and 24 months after IST of the 4 groups were not significant (P > 0.05). (3) No significant differences were found in the mortalities 4, 6, 12 and 24 months among the 4 groups (P > 0.05). (4) Of the 105 patients, 4 children had relapsed disease in the period of time from 6 to 24 months after IST. All the four patients belonged to the groups with G-CSF. (5) The use of G-CSF could not decrease the infection period before IST (day) (P = 0.273), and it had no impact on the infection rate after IST (P = 0.066). It did not reduce the rates of septicemia and infectious shock. And to the infection-related death rate no significant conclusion can be made. (6) Follow up of the patients for 13 years, showed that 2 had the evolution to MDS/AML in the 105 patients and the two children belonged to the groups with G-CSF. (7) Kaplan-meier curve analysis did not show any differences in the survival rates of the four groups. (8) Cox regression analysis showed that the use of G-CSF had no benefit to the patients' long term survival. While the age of diagnosis and the infection history before IST were significantly related to the patients' long term survival.

CONCLUSIONThe use of G-CSF did not contribute to the early response and could not reduce the infection rate, infection-related death rate and the patients' long term survival. There were no significant differences in the survival rates of the four groups. Attention should be paid to the risk of the evolution to MDS/AML.

Adolescent ; Anemia, Aplastic ; drug therapy ; immunology ; mortality ; Antilymphocyte Serum ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Cyclosporine ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; therapeutic use ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Infant ; Male ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Survival Rate ; Treatment Outcome

OBJECTIVETo evaluate the long-term outcome of immunosuppressive therapy (IST) in patients with severe aplastic anemia (SAA).

METHODSHematopoietic recovery (peripheral blood cell counts, bone marrow aspirates, bone marrow biopsy, in vitro culture of hematopoietic progenitors), immunity of T lymphocyte, quality of life and side-effects of the therapy were assessed in 50 SAA patients who have survived more than 3 years after IST.

RESULTSAt 3 years, 4 years and 5 years follow-up, 81.5% (13 cases), 86.7% (13 cases) and 89.5% (17 cases) of the SAA patients reached and maintained normal peripheral blood cell counts, 93.4% (15 cases), 93.3% (14 cases) and 94.7% (18 cases) showed normal bone marrow pictures, and 37.5% (6 cases), 40.0% (6 cases) and 73.7% (14 cases) had normal yields of bone marrow cell culture, respectively. Overall, 86.0% (43 cases), 94.0% (47 cases) and 52.0% (26 cases) of the total SAA patients were normalized in peripheral blood counts, bone marrow picture and culture of hematopoietic progenitor yields, respectively. During the follow-up, 88.0% (44 cases) of the patients achieved 100 of Karnofsky scores; 26 of the 31 patients (83.9%) who received bone marrow biopsy showed normal histological pictures, and 29 of 37 patients (78.4%) tested had normal subsets of T lymphocytes. No clonal disease was found. The late side-effects of IST were mild. All of the parameters tested were normal in 24 patients.

CONCLUSIONAfter IST, the hematopoietic function of bone marrow, the immunity of the T lymphocyte and the life quality were normalized with few side-effects in patients with SAA. These patients would probably be cured.

Adolescent ; Adult ; Anemia, Aplastic ; drug therapy ; mortality ; Blood Cell Count ; Bone Marrow Examination ; Child ; Disease-Free Survival ; Female ; Follow-Up Studies ; Hematopoietic Stem Cells ; cytology ; physiology ; Humans ; Immunosuppressive Agents ; therapeutic use ; Karnofsky Performance Status ; standards ; Male ; Middle Aged ; Recovery of Function ; physiology ; Survival Rate ; Treatment Outcome