Diagnosis and Management of Acquired Aplastic Anemia: Consensus Statement of Indian Academy of Pediatrics

Justification: In India, there is a lack of uniformity of treatment strategies for aplastic anemia (AA), and many children are managed only with supportive care due to non-availability of hematopoietic stem cell transplantation (HSCT). Process: Eminent national faculty members were invited to participate in the process of forming a consensus statement in Hyderabad in July, 2016. Draft guidelines were circulated to all members, and comments received in a online meeting in October, 2020 were incorporated into the final draft. These were approved by all experts. Objective: To facilitate appropriate management of children with acquired aplastic anemia. Recommendations: Key recommendations are: i) A bone marrow biopsy is must to make a diagnosis of AA; ii) Rule out inherited bone marrow failure syndromes (IBMFS), connective tissue disorders, viral infections, paroxysmal nocturnal hemoglobinuria (PNH), drug or heavy metal induced marrow suppression in all cases of AA; iii) Conservative approach to transfusions should be followed, with a target to keep hemoglobin >6 g/dL in children with no co-morbidities; iv) HLA-matched sibling donor HSCT is the preferred choice of treatment for newly diagnosed very severe/ severe AA; v) In absence of HLA-matched family donor, a matched unrelated donor (MUD) transplant or immunosuppressive therapy (IST) should be considered as alternate choice based on physician expertise; vi) Fludarabine, cyclophosphamide and anti-thymocyte globulin (ATG) based conditioning with cyclosporine and methotrexate as graft versus host disease (GvHD) prophylaxis is the preferred regimen; vii) Horse ATG and cyclosporine are the recommended drugs for IST. One should wait for 3-6 months for the response assessment and consideration of next line therapy.

Similar transplant outcomes between haploidentical and unrelated donors after reduced-intensity conditioning with busulfan, fludarabine, and anti-thymocyte globulin in patients with acute leukemia or myelodysplastic syndrome

BACKGROUND: Although T-cell-replete hematopoietic cell transplantation (HCT) from haploidentical donors (HIDs) using anti-thymocyte globulin (ATG) has shown promising outcomes, previous studies often adopted heterogenous graft sources and conditioning.METHODS: We retrospectively compared HCT outcomes from 62 HIDs, 36 partially-matched unrelated donors (PUDs), and 55 matched unrelated donors (MUDs) in patients with acute leukemia or myelodysplastic syndrome using the same graft source of peripheral blood and a reduced intensity conditioning of busulfan, fludarabine, and ATG.RESULTS: The estimates of 3-yr disease-free survival (DFS) and overall survival (OS) rates were not significantly different among the MUD, HID, and PUD groups, at 46%, “41%, and 36%” for the DFS rate (P=0.844), and 55%, 45%, and 45% for the OS rate (P=0.802), respectively. Cumulative incidence of relapse and non-relapse mortality at 3 yr was similar among different donor types. Subsequent multivariable analyses showed that the sex of the patient (male) and a high/very high disease risk index were independently associated with poorer DFS and OS, while the donor type was not.CONCLUSION: T-cell replete HCT from HIDs using an ATG-containing reduced intensity conditioning regimen may be a reasonable option in the absence of matched related donors in patients with acute leukemia or myelodysplastic syndrome.

Anti-thymocyte globulin in haematology: Recent developments

Anti-thymocyte globulin (ATG) is a polyclonal antiserum introduced into clinical medicine more than 30 years ago. It induces a broad non-specific immunosuppression. In haematology, standard indications are severe aplastic anaemia and prophylaxis and treatment of graft-versus-host disease (GVHD) (after allogeneic transplantation). For aplastic anaemia, ATG from horses has been found to be superior to ATG from rabbits. In the situation of allogeneic transplantation, ATG lessens the risk of chronic GVHD but may not improve survival. There is current controversy regarding which patients benefit most from ATG and what the ideal dosage is. It is likely that in the coming years a more specific immunosuppressive will be developed that will minimize GVHD while maintaining the graft-versus-malignancy effect.

Acquired amegakaryocytic thrombocytopenic purpura - An underdiagnosed entity.

Acquired Amegakaryocytic Thrombocytopenic Purpura (AATP) is a rare cause of thrombocytopenia presenting over a wide age group with symptoms of bleeding and bone marrow showing isolated absence of megakaryocytes in an otherwise normal marrow. Here, we report a case of AATP in a three year old female child who was then treated with anti thymocyte globulin successfully. We report this case because of it’s under diagnosis or misdiagnosis as immune thrombocytopenia (ITP) in most of the cases. We also review the literature regarding the pathogenesis and treatment of this undiagnosed entity.

Outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine A, / Resultado de crianças com anemia aplástica grave adquirida tratadas com globulina antitimocítica de coelho e ciclosporina A,

Objective: To evaluate the outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine as first-line treatment at this institution. Methods: Retrospective analysis of 26 pediatric patients with aplastic anemia, treated between 1996 and 2011 with rabbit antithymocyte globulin plus cyclosporine. Results: The overall response rate at six months was 34.6% (9/26), and the cumulative incidence of relapse was 26.5% (95% confidence interval [CI]: 1.4%-66%) at 5 years. The cumulative incidence of clonal evolution after immunosuppressive therapy was 8.3% (95% CI: 0.001%-53.7%) at five years with both clonal evolutions in non-responders who acquired monosomy 7 karyotype. The overall survival at five years was 73.6% (95% CI: 49.2%-87.5%). Conclusions: The present results confirm the poor response rate with rabbit antithymocyte globulin as first therapy in pediatrics patients, similar to what has been reported for patients of all ages. This confirmation is problematic in Brazil, given the lack of horse antithymocyte globulin in many markets outside the United States. .

Objetivo: Avaliar o resultado de crianças com anemia aplástica grave adquirida tratadas com globulina antitimocítica de coelho e ciclosporina como tratamento inicial em nosso instituto. Métodos: Análise retrospectiva de 26 pacientes pediátricos com anemia aplástica tratados entre 1996 e 2011 com globulina antitimocítica de coelho e ciclosporina. Resultados: A taxa de resposta geral em seis meses foi de 34,6% (9/26), e a incidência acumulada de recorrência foi de 26,5% (intervalo de confiança [IC] de 95%,1,4%-66%) em cinco anos. A incidência acumulada de evolução clonal após a terapia imunossupressora foi de 8,3% (IC 95%, 0,001%-53,7%) em cinco anos, com ambas as evoluções clonais em pacientes sem resposta que adquiriram o cariótipo com monossomia 7. A sobrevida geral em cinco anos foi de 73,6% (IC 95%, 49,2%-87,5%). Conclusões: Nossos resultados confirmam a baixa taxa de resposta com globulina antitimocítica de coelho como terapia inicial em pacientes pediátricos, da mesma forma como relatado para pacientes de todas as idades. Essa confirmação é problemática em nosso país devido à falta de globulina antitimocítica de cavalo em muitos mercados fora dos Estados Unidos, incluindo o Brasil. .

Allogeneic Hematopoietic Cell Transplantation from an HLA-mismatched Family Donor: The Current Status and Future

Traditionally, human leukocyte antigen (HLA)-mismatched hematopoietic cell transplantation (HCT) has been considered ill-advised in a routine clinical practice due to excessive serious post-transplant complications, such as graft failure, graft-versus-host disease, and prolonged immunosuppression resulting in increased fatal infections. Recent introduction of new HCT techniques, especially in the area of conditioning therapy, has improved outcomes of HLAmismatched HCT considerably. Using several regimens of reduced-intensity conditioning (RIC), it is now possible to perform allogeneic HCT in patients without HLA-matched donors in the family or in the registry from HLA-mismatched family donors. Furthermore, due to less rigorous nature of RIC therapy, elderly patients (up to 70 years of age) and patients who have been treated heavily especially with a previous HCT can also be treated. In this review, we gave a brief historical background for the development of allogeneic HCT, discussed rationale for the use RIC for HLA-mismatched HCT, and summarized trial results of HLA-mismatched HCT after RIC. Lastly, future areas of research regarding HLA-mismatched HCT were discussed.

A Case of C4d-Positive Acute Humoral Rejection Treated with Rituximab and Plasma Exchange / 대한신장학회잡지

Although acute humoral rejection is a major cause of renal allograft loss, the diagnosis and treatment of acute humoral rejection have been very difficult because of lack of proper diagnostic tools and effective therapeutic modalities. Recently C4d deposition in peritubular capillaries of renal allografts has been demonstrated to be a sensitive and diagnostic in-situ marker of humoral rejection that correlates strongly with the presence of circulating donor-specific antibodies. Whereas conventional immunosuppressive agents are effective for the treatment of cellular rejection, specific therapeutic strategies targeting the humoral limb of immunosuppression should be necessary for the treatment of humoral rejection. Here we report a case of acute humoral rejection diagnosed with C4d immunostaining from transplant kidney biopsy and treated successfully with combination of plasma exchange, polyclonal rabbit anti-thymocyte globulin, and rituximab.

Clinical value of induction therapy with preoperative single-bolus high-dose ATG in sensitive renal transplant recipients / 中华泌尿外科杂志

0.05).The graft function of high dose group returned to normal within 3 to 7 days after operation.Delayed recovery of graft function occurred in 2 cases of routine dose group;in 1 case it returned to normal on the 21st day after operation, in the other the serum creatinine level fell down to 300 ?mol/L on the 45th day.There was no severe adverse event such as fever,chill,headache,heart-throb,dyspnea during ATG intravenous perfusion.And no serious infection occurred in the 2 groups during the first 3 months postoperatively.Hepatic function damage occurred in 1 case of high dose group.Follow-up ranged from 4 to 14 months.All recipients of high dose group survived with good graft function;5 of them could do housework. Only one graft lost its function in routine dose group. Conclusions On the basis of optimal selection of the donor and recipient,preoperative single-bolus high-dose ATG is effective and safe for the sensitive recipients as immune induction therapy, which may become one of the new induction treatments before transplantation.