Cases Of Severe Aplastic Anemia Research Articles

Severe Aplastic Anaemia in a 14-year-old boy

Aplastic anemia is a disorder of bone marrow failure characterized by pancytopenia and hypocellular bone marrow. We report a case of severe aplastic anemia in a 14-year-old boy.

Efficacy and safety of allogeneic hematopoietic stem cell transplantation in the treatment of 28 patients with hepatitis-related aplastic anemia

Objective: To evaluate the efficacy and safety of HLA-haploidentical hematopoietic stem cell transplantation (allo-HSCT) for hepatitis-related aplastic anemia (HRAA) patients. Methods: Retrospective analysis was performed on hepatitis-associated aplastic anemia patients who received haplo-HSCT at our center between January 2012 and June 2022. October 30, 2022 was the final date of follow-up. Results: This study included 28 HRAA patients receiving allo-HSCT, including 18 males (64.3% ) and 10 females (35.7% ), with a median age of 25.5 (9-44) years. About 17 cases of severe aplastic anemia (SAA), 10 cases of very severe aplastic anemia (VSAA), and 1 case of transfusion-dependent aplastic anemia (TD-NSAA) were identified. Among 28 patients, 15 patients received haplo-HSCT, and 13 received MSD-HSCT. The 2-year overall survival (OS) rate, the 2-year failure-free survival (FFS) rate, the 2-year transplant-related mortality (TRM) rate, the 100-day grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) cumulative incidence rate, and the 2-year chronic graft-versus-host disease (cGVHD) cumulative incidence rate were 81.4%, 81.4% (95% CI 10.5% -20.6% ), 14.6% (95% CI 5.7% -34.3% ), 25.0% (95% CI 12.8% -45.4% ), and 4.2% (95% CI 0.6% -25.4% ), respectively. After transplantation, all patients had no significant liver function damage. Compared with the MSD-HSCT group, only the incidence of cytomegaloviremia was significantly higher in the haplo-HSCT group [60.0% (95% CI 35.2% -84.8% ) vs 7.7% (95% CI 0-22.2% ), P=0.004]. No statistically significant difference in the Epstein-Barr virus was found in the 2-year OS, 2-year FFS, 2-year TRM, and 100-day grade Ⅱ-Ⅳ aGVHD cumulative incidence rates and 2-year cGVHD cumulative incidence rate. Conclusion: Allo-HSCT is safe and effective for HRAA, and haplo-HSCT can be used as a safe and effective alternative for newly diagnosed HRAA patients who cannot obtain HLA-matched sibling donors.

A clinical analysis of Candida tropicalis bloodstream infections associated with hematological diseases, and antifungal susceptibility: a retrospective survey.

To assess the clinical features and outcomes of hematological disease patients with Candida tropicalis bloodstream infections and determine the antifungal susceptibility of C. tropicalis. This is a retrospective, single-center, observational study conducted in the Department of Hematology at The First Affiliated Hospital of Guangxi Medical University from January 2013 to December 2021. A total of 26 hematological disease patients with C. tropicalis bloodstream infections were enrolled, and their clinical features, treatment plans, and prognoses were assessed. Univariate analysis was performed by Kaplan-Meier analysis and multivariate analysis was conducted using a Cox regression model. The antifungal susceptibility of C. tropicalis was determined from patient blood cultures. The patients had a mean age of 35 years (range: 10-65 years), 50% were male (13/26) and 88.5% had hematologic malignancies (23/26) while the remaining three patients included two cases of severe aplastic anemia and one case of β-thalassemia. All patients had neutropenia. Seven patients were initially given azole alone (26.9%), five of whom failed treatment and died (71.4%). Fifteen patients were treated with echinocandin (57.7%), three of whom failed treatment and died (20.0%), and eight patients were treated with amphotericin B (30.8%), two of whom failed treatment and died (25.0%). The total and attributable mortality rates were 42.3 and 34.6%, respectively. Univariate analysis showed that there are six risk factors for attributable deaths among hematological disease patients with C. tropicalis blood infections. These risk factors included septic shock, Pitt bacteremia scores ≥4, procalcitonin levels ≥10 ng/mL, positive plasma (1,3)- β-D glucan assay, serum albumin levels <30.0 g/L, time from fever to antifungal treatment initiation ≥5 days and time between neutropenia and antifungal treatment ≥10 days. Moreover, skin and mucosal infections and a treatment schedule that included amphotericin B and drug combinations are protective factors for attributable deaths. Multivariate analysis showed that septic shock (p = 0.006) was an independent risk factor for attributable death. All isolates were sensitive to flucytosine and amphotericin B. The intermediate or resistance of C. tropicalis to fluconazole, itraconazole and voriconazole were 41.7, 50, and 41.7%, respectively. Hematological disease patients with C. tropicalis bloodstream infections had a high mortality rate, and early antifungal therapy significantly reduced mortality. Candida tropicalis was highly resistant to azole drugs and sensitive to flucytosine and amphotericin B. According to our study, the preferred agent is amphotericin B and drug combinations should be considered for severe infections.

Post-transplant Hemophagocytic Lymphohistiocytosis in Benign Hematological Disorders: Experience of 4 Cases with Review of Literature.

Post transplant Hemophagocytic lymphohistiocytosis (HLH) is a form of secondary HLH, which can be either early onset or late onset and is associated with significant morbidity and mortality. With the increasing popularity of post transplant cyclophosphamide based haploidentical stem cell transplantation (SCT), post transplant HLH is becoming a significant complication especially in benign hematological disorders. Methods: We present 4 cases of post transplant HLH occurring in 2 cases of severe aplastic anemia (post haploidentical SCT) and 2 cases of thalassemia major (post matched sibling SCT). All 4 cases had early onset variety with dismal prognosis. Conclusion: Post-transplant HLH is an important entity in benign hematological disorders, which needs to be identified early and treated promptly with steroids, monoclonal agents or immunosuppressive therapy. Serum ferritin levels are an important biomarker and help in monitoring response.

Clinical features and risk factors of hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

目的探讨异基因造血干细胞移植（allo-HSCT）患者出血性膀胱炎（HC）发生的相关因素、治疗措施和预后。方法对2010年1月1日至2017年5月31日期间425例接受allo-HSCT的患者进行回顾性分析。结果①全部425例患者中，男262例，女163例，中位年龄26（2~56）岁；急性髓系白血病（AML）138例，急性淋巴细胞白血病（ALL）96例，骨髓增生异常综合征（MDS）29例，重型再生障碍性贫血（SAA）98例，慢性髓性白血病（CML）64例；同胞全相合移植221例，无关供者移植89例，单倍型移植115例。②108例（25.41%）患者发生HC，中位发生时间为移植后32（3~243）d，中位持续时间20（3~93）d；Ⅰ级33例（30.56%），Ⅱ级49例（45.36%），Ⅲ级21例（19.44%），Ⅳ级5例（4.63%）。③108例发生HC的患者中，103例治愈，5例无效，12例患者死于移植相关并发症（感染、复发、重度急性GVHD、继发植入失败）。④单因素分析显示：年龄<30岁、移植类型、CMV血症、急性GVHD与HC发生有相关性。多因素分析显示，急性GVHD是allo-HSCT患者发生HC的独立危险因素。结论allo-HSCT后合并HC患者的总体预后较好。

Successful Treatment with Intrathecal Tocilizumab(IL-6 antibody) for 2 Cases of Graft-Versus Host Disease of the Central Nervous System after a Second Allogeneic HSCT from Haploidentical Donor

Graft-versus-host disease (GVHD) of central nervous system (CNS) is a rare complication after allogeneic hematopoietic cell transplantation (allo-HSCT), which is easily misdiagnosed and has limited treatment and poor efficacy. In this study, we reported two children(1 case of severe aplastic anemia and 1 case of acute myeloid leukemia) who were subjected to the secondary haploid hematopoietic stem cell transplantation of another door after the first implantation failure. Two patients developed epileptic seizures during hematopoietic recovery. Peripheral blood and cerebrospinal fluid cytokines were detected and diagnosed as acute GVHD in the central nervous system. The cytokine elevation is mainly IL-6(IL-6 level in peripheral blood was 2276.25 pg/ml, and in cerebrospinal fluid was 2353.89pg/ml of case 1). We administered multiply consecutive plasmapheresis, intravenous infusion of tocilizumab combined with intrathecal injection of tocilizumab and dexamethasone. The epileptic symptoms of 2 cases are effectively controlled after the first dose. The IL-6 levels in peripheral blood and cerebrospinal fluid of both patients decreased significantly after 4(IL-6 level in peripheral blood was 6.74 pg/ml, and in cerebrospinal fluid was 195.72pg/ml of case 1) and 5 doses, respectively. Central nervous system aGVHD is prone to hematopoietic recovery after secondary transplantation; intrathecal injection of tocilizumab is safe and effective in the treatment of central nervous system aGVHD with elevated IL-6 mainly, which is worth further exploring. DisclosuresNo relevant conflicts of interest to declare.

Molecular alterations in the TCR signaling pathway in patients with aplastic anemia.

BackgroundA previous study has demonstrated a significantly increased CD3ζ gene expression level in aplastic anemia (AA). However, the mechanism underlying the upregulated CD3ζ mRNA expression level and that of T cell activation signaling molecules in AA patients remains unclear. Thus, we investigated the expression levels of the CD3ζ, CD28, CTLA-4, and Cbl-b genes, the SNP rs231775 in the CTLA-4 gene, and the distribution of the CD3ζ 3′-UTR splice variant in AA patients.MethodsCD3ζ 3′-UTR splice variants were identified in peripheral blood mononuclear cells (PBMCs) from 48 healthy individuals and 67 patients with AA [37 cases of severe aplastic anemia (SAA) and 30 cases of non-sever aplastic anemia (NSAA)] by RT-PCR. CD3ζ, CD28, CTLA-4, and Cbl-b gene expression was analyzed by real-time quantitative PCR. The SNP rs231775 in CTLA-4 gene was analyzed by PCR-RFLP.ResultsCD3ζ and CD28 expression was significantly higher, while CTLA-4 and Cbl-b expression was significantly lower in AA patients compared with healthy individuals. Significantly higher CD3ζ expression was found in the NSAA subgroup compared with the SAA subgroup. 64 % of the AA samples had the same genotype (WT+AS+CD3ζ 3′-UTR); 22 % of the AA patients had a WT+AS−CD3ζ 3′-UTR genotype, and 14 % of the AA patients had a WT−AS+CD3ζ 3′-UTR genotype. The CD3ζ expression level of WT−AS+ subgroup was the highest in the SAA patients. A significantly higher frequency of the GG genotype (mutant type, homozygous) of SNP rs231775 in CTLA-4 gene was found in the AA patients. Positive correlation between the CTLA-4 and Cbl-b gene expression levels was found in healthy individuals with the AA and AG genotypes, but not in the AA patients.ConclusionsThis is the first study analyzing the expression characteristics of the CD28, CTLA-4, and Cbl-b genes in AA. Our results suggest that aberrant T cell activation may be related to the first and second signals of T cell activation in AA. The GG genotype of SNP rs231775 in CTLA-4 gene might be associated with AA risk in the Chinese population. The characteristics of CD3ζ 3′-UTR alternative splicing may be an index for evaluating the T cell activation status in AA patients, particularly in SAA patients.

Clinical analysis of allogeneic hematopoietic stem cell transplantation for treatment of 71 cases of severe aplastic anemia

Clinical analysis of allogeneic hematopoietic stem cell transplantation for treatment of 71 cases of severe aplastic anemia

ミオクロニー失立発作てんかんに対するエトスクシミドにより重症型再生不良性貧血を来した症例

ミオクロニー失立発作てんかんに対するエトスクシミドにより重症型再生不良性貧血を来した症例

Aplastic Anemia: Effectiveness and Safety of Treatment Profiles Depending On Age

AbstractAbstract 4407 Introduction:The treatment of acquired aplastic anemia (AA) is based on allogeneic hematopoietic cell transplantation (HCT) and immunosuppressive therapy (IST). The choice between immunosuppression or HCT is based on the availability of a sibling donor and on the patient's age. According to the PETHEMA group's guidelines for the diagnosis and management of aplastic anaemia, patients over 40 years old are not considered for HCT as first-line therapy, while there is no age limit for immunosuppressive treatment. The decision of whether to treat older patients is based on their performance status. Aims:To compare the safety and effectiveness of treatment profiles, mortality rates and causes of death in adults with AA depending on age (over or under 60 years old). Methods:We reviewed clinical histories of patients who have been treated for AA at our hospital over the last ten years (2002–2012). Patients were divided in to 2 groups: over 60 year olds and under 60 year olds. We collected data on age, sex, disease severity, treatment protocols and toxicities, type and duration of response to therapy, mortality and cause of death. Data source: clinical histories. Statistical desciption, non inferential because of the low level of patients. Results:We identified 15 patients in total, 7 over 60 and 8 under 60 years old. One of the over 60 year olds was excluded from the study due to incomplete follow-up. Of the 6 remaining over 60 year old patients all were female and they had a median age of 73 years (r, 63–87 years), while in the under 60 group, 50% of the patients were male with a median age of 30.5 years (r, 19–49 years).50% of the over 60 year olds had a Charlson Index score of 2 or more. The Charlson index in the under 60 year olds was 0, with the exception of 1 subject (11.1%) with a score of 2 (due to chronic lung and liver disease).We observed a higher rate of moderate AA in the under 60 year olds (62.5% vs 50%) and 1 case of severe AA and 2 cases of very severe AA in each group respectively.100% of over 60 year olds received treatment with ciclosporin (CsA) in combination with other immunosuppresant drugs (in 3 cases associated with antithymocyte-globulin (ATG) and corticosteroids). After a median follow-up of 300 days (r, 90–1044 days), only 1 patient of the 6 responded to therapy, obtaining a partial response (PR) which lasted 953 days.In the under 60 group 2 of the patients (25%) recieved an allogeneic HCT obtaining a complete response (CR) in both cases, which they maintain after a median follow-up of 1870 days (r, 1781–1960 days). The remaining 75% received treatment with IST. In this group we observed 2 CR, 3 PR and one non-responder. All responses are maintained after a median follow-up of 1038 days.Toxicities observed in the over 60s consisted of 3 cases of diabetes mellitus, 1 case of renal failure and 3 severe infections in three different patients, while 62.5% of the under 60s suffered from infectious complications.In the over 60 year old group we observed 3 cases of exitus (50%). At 15 months global survival was of 40% for non-responders, clearly inferior to the survival of the only responder. However in the under 60 year old group there was only 1 case of exitus corresponding to the non-responder and a global survival of 87.5% after a median follow-up of 1602 days (r, 643–3094). Conclusion:Treatment of AA in patients under 60 years old is effective and safe. The incidence of serious adverse events and mortality rates are low. Survival is superior in patients treated with HCT than in those treated with IST. Outcomes of IST are related to patient age. Response rates in over 60 year olds are low, although the higher survival rates in responders clearly support the indication of IST. Disclosures:No relevant conflicts of interest to declare.

Cotransplantation of Allogeneic Mesenchymal and Hematopoietic Stem Cells in Children With Aplastic Anemia

We report here the preliminary results of allogeneic hematopoietic stem cell transplantation with mesenchymal stem cells (MSCs) for 6 cases of severe aplastic anemia. The patients ranged in age from 3 to 16 years, and the median time from diagnosis to transplantation was 32 months (range: 3-156 months). The conditioning regimens consisted of fludarabine, cyclophosphamide, and antithymocyte globulin with or without busulfan. Graft-versus-host disease (GvHD) was prevented by the administration of cyclosporine A, methotrexate, and mycophenolate mofetil, with or without anti-CD25 monoclonal antibody. The grafts were granulocyte colony-stimulating factor-mobilized bone marrow and peripheral blood from HLA antigen-haploidentical donors (3 cases) or peripheral blood only from unrelated HLA antigen-identical donors (3 cases). MSCs were intravenously injected at a median dose of 1.43 × 10(6)/kg (range: 0.85-2.5 × 10(6)/kg). The mean time for neutrophil and platelet recovery was 12.3 and 13.8 days, respectively. Acute GvHD grade I and II developed in 2 cases, and no chronic GvHD was documented. All patients were alive and transfusion independent at a median follow-up of 15 months (range: 6-29 months). Our report suggests that cotransplantation of allogeneic hematopoietic stem cells and MSCs might provide an opportunity for therapy for children with severe aplastic anemia.

Acute Parvovirus B19 Infection Leading to Severe Aplastic Anemia in a Previously Healthy Adult Female

Human Parvovirus B19 has been linked to a variety of diseases. One of the most common complications is transient aplastic crisis in patients with chronic hemolytic anemia. Very few case reports have implicated this virus as a putative etiology behind hepatitis and severe aplastic anemia in immuno competent individuals. We report a case of severe aplastic anemia in a previously healthy adult female due to acute parvovirus B19 infection. Laboratory examination showed pancytopenia in peripheral blood and severe hypoplastic bone marrow on biopsy. Serological analysis (ELISA) revealed acute Parvovirus B19 infection. In the face of unavailable HLA matched bone marrow donor, immuno-supressive therapy was contemplated, but could not be given because of financial constraints. Pancytopenia persists till date, 4months after the diagnosis, with the patient requiring repeated packed red cell and irradiated platelet transfusions. Thus, acute infection with this virus must be considered a cause of acquired aplastic anemia even in individuals without underlying disease.

Diagnosis and outcome of neutropenic enterocolitis: experience in a single tertiary pediatric surgical center in China

Neutropenic enterocolitis (NE) is clinically defined by the triad of neutropenia, abdominal pain and fever. This retrospective study is to review 24 cases of NE in a single Chinese tertiary center, to elucidate clinical feature, treatments and outcome for this dangerous gastrointestinal complication of neutropenia. The medical records of pediatric patients who were diagnosed with neutropenic enterocolitis from 2000 to 2009 were reviewed. Of 24 cases, the ratio of male to female was 2:1, the mean age was 7.2 years. There were eight cases of acute lymphocytic leukemia, eight cases of acute non-lymphocytic leukemia, four cases of non-Hodgkin's lymphoma, one case of severe aplastic anemia, one case of neuroblastoma and two cases of simple neutropenia without underlying cause. The hematologic malignancy was significantly associated with the occurrence of NE (OR = 19.4). Seventeen cases developed NE during anticancer chemotherapy (chemo group), four cases presented with leukemia and one case presented with aplastic anemia before the initiation of chemotherapy and their presenting event leading to diagnosis. Two cases simply presented with NE without definitive reasons (no chemo group). All the patients had the typical clinical presentation, six cases had disseminated peritonitis, toxic shock, and assisted ventilations were necessary in three of these six cases. CT or ultrasound demonstrated bowel wall thickness, paucity of air in the cecum and/or right colon, pneumatosis or pneumoperitoneum. There was no difference in the nadir neutrophil count in patients, who received chemotherapy versus those who did not (P = 0.001), but the recovering time from NE in chemo group (9.3 ± 1.9) was shorter than non-chemo group (10.7 ± 5.3, P = 0.034). Sixteen (88.8%) cases have been successfully managed medically, using aggressive hemodynamic support, bowel rest, and broad-spectrum antibiotic therapy with surgical intervention reversed only for the more severe six cases (25%). Two cases died. NE is a life-threatening gastrointestinal complication of neutropenia. Physicians might remain vigilant and consider NE in any neutropenic patient rather than only in oncologic patients. It has typical clinical presentation and CT can provide clear delineation for diagnosis. Early recognition and progressed management have reduced mortality. Most children with NE may be treated without surgery with favorable outcome.

Paroxysmal nocturnal hemoglobinuria and pregnancy before the eculizumab era: the French experience

Pregnancy in women with paroxysmal nocturnal hemoglobinuria is rare, with few reports on maternal and fetal mortality rates. A specific questionnaire designed to solicit data on pregnancies in women with paroxysmal nocturnal hemoglobinuria was sent to all members of the French Society of Hematology in January 2008. We identified 27 pregnancies in 22 women at 10 French Society of Hematology centers between 1978 and 2008. The median age was 21.5 years at diagnosis of paroxysmal nocturnal hemoglobinuria and 27 years at pregnancy. None of these women had received eculizumab during their pregnancy. Maternal complications, consisting mostly of cytopenias requiring transfusions, occurred in 95% of cases. Two cases of severe aplastic anemia (de novo in one case and relapse in the other) were recorded. No thrombotic events occurred during pregnancy, whereas 4 postpartum thromboses (16%) were recorded, 2 of which were fatal (maternal mortality rate 8%). Most patients received antithrombotic prophylaxis during pregnancy and postpartum (n=16; 64%). Delivery was preterm in 29% of cases, and birth weight was less than 3 kg in 53% of cases. Fetal mortality rate was 4%. Pregnancy during paroxysmal nocturnal hemoglobinuria is associated with increased maternal and fetal mortality rates (8% and 4%, respectively, in this series). Maternal mortality is related to postpartum thromboses. Prophylactic anticoagulation is recommended during pregnancy and for six weeks postpartum.

Successful immunosuppressive and iron chelation therapy for a severe aplastic anemia patient undergoing hemodialysis due to chronic renal failure

Immunosuppressive treatment using antithymocytic globulin (ATG) is the treatment of choice for severe aplastic anemia patients [1, 2]. Iron chelation therapy is also effective for patients with frequent blood transfusions [3–5]. However, the effects of these treatments on hemodialysis patients have not been reported. Here, we present a case of severe aplastic anemia on hemodialysis, treated with immunosuppressive and iron chelation therapy. A 49-year-old male presented in December 2007 with fever and pancytopenia. He required regular hemodialysis following history of chronic renal failure 25 years earlier, and had also been treated with recombinant epoetin beta. Laboratory studies revealed a white blood cell count of 1.2 9 10/ll, neutrophil cell count of 468/ll, platelet count of 0.9 9 10/ll, hemoglobin concentration of 5.4 g/dl, and reticulocytes at only 0.9 9 10/ll. Bone marrow biopsy revealed severe hypoplasia. He was diagnosed with severe aplastic anemia, and required frequent transfusions of PC and RBC to maintain a 2 9 10/ll platelet level and 8.0 g/dl hemoglobin concentration. He was given the antibiotic, meropenem, for febrile neutropenia, which rapidly controlled his fever. The same drug, epoetin beta, was continued for treatment. Cyclosporin A and granulocyte colony-stimulating factor (G-CSF) were given as the first therapy for severe aplastic anemia, but his bone marrow remained hypoplastic. Horse ATG was added at a dose of 15 mg/kg for 5 days. Methylprednisolone was used at a dose of 2 mg/kg/day for 5 days, and then tapered off. The only adverse event was a grade 2 allergic reaction. His hematopoietic system recovered slightly, and G-CSF was lowered, but transfusion frequency could not be reduced. An anabolic steroid was added, but yielded no improvement. Then, 8 months after the first ATG, a second rabbit ATG was given at a dose of 5 mg/kg for 5 days. Methylprednisolone was given concomitantly, and no significant adverse event was seen, except an acute allergic reaction. Total red-blood cell transfusion volume was over 80 Japanese units, so deferasirox was given. Bone marrow biopsy revealed a moderate number of positive granules on iron staining, which were not observed at the initial examination. The initial dose was 10 mg/kg/day, due to renal failure, but the serum ferritin level remained above 3000 ng/ml. The dose was increased to 20 mg/kg/day. Six months later, the serum ferritin level was below 1000 ng/ml. Transfusion frequency was reduced. One year later after the second ATG therapy, he became transfusionfree (Fig. 1). Bone marrow biopsy revealed the recovery of hematopoiesis, but on iron staining, a moderate number of positive granules were still observed. During this course of treatments, he continued dialysis three times per week in an open space, and bacterial infection was not a threat. J. Hiraga (&) R. Sakemura S. Mizuno Department of Hematology, Toyota Memorial Hospital, 1-1 Heiwa-cho, Toyota 471-8513, Japan e-mail: junji_hiraga@mail.toyota.co.jp

繰り返し大量methylprednisolone (M-PSL) パルス療法を施行した重症再生不良性貧血の3症例

繰り返し大量methylprednisolone (M-PSL) パルス療法を施行した重症再生不良性貧血の3症例

A case of severe aplastic anemia secondary to treatment with lenalidomide for multiple myeloma

Lenalidomide is an important contemporary treatment option for patients with multiple myeloma (MM). Rare instances of autoimmune conditions have been observed in association with its use. Although moderate myelosuppression is not uncommonly seen in patients treated with lenalidomide, aplastic anemia has not previously been reported to be associated with this agent. We describe a case of severe aplastic anemia (AA) that was probably induced by lenalidomide. A 64-year-old male patient developed progressive pancytopenia three weeks into therapy with lenalidomide for his relapsed MM. A bone marrow aspirate and biopsy confirmed the diagnosis of AA and suggested the existence of an immunological reaction at the level of marrow. A gradual spontaneous recovery of normal hematopoiesis followed after the lenalidomide discontinuation.

Short Term Outcome after Allogeneic Stem Cell Transplantation in 70 Cases of Severe Aplastic Anaemia.

Allogeneic stem cell transplantation (SCT) from HLA matched sibling donor is the standard treatment option in younger patients with severe aplastic anaemia (SAA). In the current study outcome of 70 patients with SAA undergoing allogeneic SCT at our institution from July 2001 to June 2007 is presented. Median follow up time was 727 days (range 100–2187). Three patients received 2nd SCT due to graft failure or rejection so actual number of SCT in the patients was 73. Median age of the patients was 16 years (range 5–38), 55 males, and 15 females. Seventeen had major ABO mismatch while sex mismatch in the form of female donor to male patient was present in 23 cases, 7 had both major ABO and sex mismatch. Sixty four patients were CMV positive while 6 had CMV negative status. Conditioning regimens included; cyclophosphamide (Cy) 200 mg/kg with either antilymphocyte globulin (ALG) 45 mg/kg (n=33) or antithymocyte globulin (rabbit ATG) 11.25 mg/kg (n=26); Cy plus Campath 100 mg (n=6), fludarabine 150 mg/m2 plus Cy 300 mg/m2 and ATG (n=8). All patient undergoing 2nd transplant received conditioning with Cy, fludarabine and ATG. GVHD prophylaxis was given with cyclosporin (CSA) plus prednisolone (41) with or without short course of methotrexate (29). Patients received PBSC (10) or bone marrow (12) alone or both (48). Mean mononuclear and CD34+ cell doses were 5.59 x 108/Kg and 4.8 x 106/Kg respectively. Median time to neutrophil recovery was 11 days (range 7–24). Neutropenic fever was seen in 60% cases, with mean duration of fever being 8 days. In majority (66%) no focus of infection could be found. Various isolates included gram negative rods (n=6), staphylococcus (n=2) and fungi (n=5). Other post-transplant infections were tuberculosis (n=2), herpes zoster (n=2) and transfusion associated falciparum malaria (n=2). Post-BMT non-infectious complications included acute GVHD (24%), chronic GVHD (08%), hemorrhagic cystitis (14%), seizures (5%), and VOD (3%). Graft rejection and primary graft failure was seen in 3 and 2 cases respectively. Three of them received 2nd transplant and had successful recovery while the other 2 died of septicemia. Six patients died during peri-transplant period, 3 at day 100, and 8 beyond day 100. One patient died of unrelated cause at 2 years post-transplant. Main causes of death were septicemia (n=4), conditioning regimen toxicity (n=3), VOD (n=2), GVHD (n=2) and disseminated aspergillosis (n=2). The overall and disease free survival was 76%. In univariate analysis using Logrank and Wilcoxon test factors correlated with better survival were patient's age <15 years, disease duration <6 months, previous transfusions <20 events, conditioning with fludarabine/Cy/ATG, and absence of chronic GVHD. SCT from HLA matched sibling donor is effective treatment modality in majority of the young patients with SAA.

Severe aplastic anemia in children

A Severe Aplastic Anemia is a rare disease that happens in the entire world. Because the rarity, it is difficult to characterize the features of the patients that have this disease, and to find their possible etiological factors. To report all cases of severe aplastic anemia in young people who were attended in the hospital and characterize some variables like age, sex, geographic area of residence, etiologies and socioeconomic status. It was done a descriptive analyze of all pediatric patient's features (below 18 years) who came to the hospital in 1979-1993 with severe aplastic anemia based on the classification proposed for Camitta et al. The data were obtained from the hospital records in 134 children, and the investigator in 79 families performed interviews. The age ranged from 2-18 years (mean 10.89 years). The male to female ratio was 64:70. Most of the patients came from urban zone of south Brazil. We did not identify any etiologic agents in 34% of the cases. Prior exposure to the agricultural pesticides and benzene derivative was the most common etiologic factors that were related. The household income of 83.5% of the families was < $ 65 U.S./capita, and 70.9% of the patient's mother did not finish the primary school CONCLUSION. In this group, severe aplastic anemia is more frequent in 11 years old girls. Most of them are the in urban zone of south Brazil, with low socioeconomic status, and related prior exposure agricultural pesticides and benzene derivative.

The simplification of the SCT procedures in developing countries has resulted in cost-lowering and availability to more patients.

In order to simplify and cutting down expenses of the bone marrow transplantation procedures we have made some efforts, trying to provide the best transplantation technique for the individual patient with scarce resources. In relation with the source of stem cells, we have found very attractive the use of peripheral blood stem cells (PBSC) instead of bone marrow cells. This procedure can produce substantially more rapid engraftment than observed with bone marrow. The rapid hematopoietic reconstitution in the recipient of PBSC lower expenses stemming from the use of antibiotics, blood bank products and days at the hospital. In Mexico, a country with a large number of cases of severe aplastic anemia we decided to use PBSC to transplant 10 patients with this disease, in order to take advantage of the large number of stem cells that this procedure can provide. We had excellent results in these patients, avoiding the high cost of the conventional transplantation and the use of ATG. In relation to autologous transplantation we have made efforts to perform autografts without the use of freezing devices, keeping the stem cells in liquid form using a conventional blood bank refrigerator for up to 96 hr. This modifications have resulted in diminishing costs and increasing the availability of the procedure to a large number of patients. Finally in Mexico we have had experience with non-myeloablative transplants, and obtained reasonably good results, with a median cost of 18,000 USD per allogeneic transplantation procedure. In some cases this is the only affordable therapeutic option. In developing countries where very few patients can afford the cost of conventional bone marrow transplants, any reasonable effort in the direction of simplification must be welcome.