Fludarabine‐based reduced intensity conditioning regimens for allogeneic hematopoietic stem cell transplantation in patients with aplastic anemia and fungal infections

Abstract

Eighteen patients (12 men and 6 women) with aplastic anemia and active fungal infections (10 proven/probable; 8 possible) underwent stem cell transplantation using fludarabine combined with cyclophosphamide or total body irradiation. Peripheral blood stem cells (PBSC) were the main graft source and a combination of cyclosporine with either methotrexate or methylprednisolone was used for graft versus host disease prophylaxis. Fourteen patients (77.8%) achieved neutrophil engraftment after a median time of 11 d, while four died of fungal sepsis. Resolution of fungal infection occurred in 60% of patients with proven/probable infections and in 100% with possible fungal infections. At a median follow up of 30 months, 11 patients (61.1%) were alive and well. Fludarabine-based conditioning regimens with PBSC transplantation can be used successfully in patients with aplastic anemia and fungal infections.

Comparing Outcomes with Bone Marrow or Peripheral Blood Stem Cells as Graft Source for Matched Sibling Transplants in Severe Aplastic Anemia across Different Economic Regions

“…Studies from less economically developed countries suggest that because of delays in HSCT, patients in these countries are multitransfused with high risk of graft rejection and may be infected with high risk of graft rejection and may be infected at the time of HSCT. 7,8,38,39 Patients are also at higher risk due to CMV positivity present in almost 100% donors and recipients in many of these countries. 39-41 Leucodepletion of blood is uncommon in LIC.…”

“…45,46 Funding is through sponsorship by government, non-governmental organizations (NGOs) and charitable organizations. 6,7,38,40,44 Delay in engraftment or in resolution of infections would lead to exhaustion of funds for further treatment leading to fatality. Hence, unlike in HIC where patients can be supported for long periods of time, limited funds compel transplant programs for the fastest engraftment and independence from blood component transfusions as well as control of infections.…”

“…Most centers use G-CSF to hasten neutrophil recovery. 7,8 The adverse consequence of PBSC use would be a greater risk of chronic GVHD and hence a higher cost of treating this complication. For patients paying out of pocket, managing costs of chronic GVHD spread over time may be easier than arranging immediate finances for a complicated transplant admission.…”

The use of a fludarabine‐based conditioning regimen in patients with severe aplastic anemia – a retrospective analysis from three Indian centers

“…To reduce the risk of graft failure and improve outcome, modification of conditioning regimens using a fludarabine‐based conditioning has been attempted in a number of small studies . We have reported previously along with other groups the utility of using fludarabine‐based regimens in both heavily transfused patients as well as in patients with active infection at the time of HSCT . Fludarabine‐based regimens have also been used in patients undergoing unrelated stem cell transplants for SAA and as conditioning in older patients with SAA .…”

Successful Allogeneic Bone Marrow Transplantation Using Reduced Doses of Cyclophosphamide and Fludarabine Associated to Granulocyte Transfusions in a Patient With Severe Aplastic Anemia Complicated by an Invasive Aspergillosis of Sinuses and a Rhizopus Gingivitis

“…Profound neutropenia and the long delay between diagnosis and BMT were the principal host risk factors she had. 15 The only antifungal therapy was unable to control infection unless neutropenia was resolved by allogeneic BMT-associated to G-CSF use and granulocyte transfusions reported to help control infection until engraftment occurs. There are some reports on breakthrough zygomycosis developed under voriconazole.…”