Long-Term Outcome after Bone Marrow Transplantation for Aplastic Anemia Using Cyclophosphamide and Total Lymphoid Irradiation as Conditioning Regimen

Abstract

We retrospectively studied 49 patients in a single institute to evaluate the long-term outcome of total lymphoid irradiation (TLI) conditioning for allogeneic stem cell transplantation (allo-SCT) to treat aplastic anemia (AA). Most of the patients had received transfusions and had undergone previous treatment, with 33 receiving related transplants and 16 receiving unrelated transplants. Conditioning consisted of cyclophosphamide (Cy; 200 mg/kg) plus TLI (750 cGy) for related transplantation and Cy plus total body irradiation (TBI; 500 cGy) and TLI (500 cGy) for unrelated transplantation. Antithymocyte globulin (ATG) was added for 6 of the unrelated transplantations. Graft-versus-host-disease (GVHD) prophylaxis consisted mainly of cyclosporine (CSA) and methotrexate (MTX). Graft failure developed in 2 patients (4.1%). With a median follow-up of 7 years, overall survival (OS) was 81% and was not statistically significantly different between the patients receiving related transplants and those receiving unrelated transplants. In multivariate analyses, a history of previous treatment with ATG was the sole factor associated with a worse survival rate, and the interval from diagnosis to treatment was not prognostic. The incidence of acute (grade II to IV) GVHD (aGVHD) was 23%, and that of chronic GVHD (cGVHD) was 29%. Female-to-male transplantation was the sole factor associated with chronic GVHD. B cell lymphoproliferative disorder developed only after the ATG-containing conditioning. No other secondary malignancies developed after long-term follow-up. Our findings suggest that TLI conditioning is feasible and effective for patients with AA.

Favorable Outcomes in Patients Surviving 5 or More Years after Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies

“…The incidence of acute and /or chronic GVHD was 30-70% in patients with hematologic diseases undergoing allogeneic SCT (33-35). The development of chronic GVHD appears to be important in reducing relapses after SCT (36).…”

Decision-Making and Problem Solving

“…15,16,20,24 A consecutive enrolment was stated in 3 23,25,27 of 13 retrospective case series. 10,11,17,[21][22][23]25,[27][28][29][30][31][32] Transplantations were performed between 1981 and 2006.…”

“…A median of 32 patients (range 11-349, total 1,645) were investigated in the total study population of 14 studies 11,[15][16][17][21][22][23][25][26][27][28][29]31,32 and in 8 relevant subgroups of 4 other studies. 10,20,24,30 The patients' median age in the individual studies was between eight and 27 years and the ratio of males : females ranged from a male (30 : 10) to a female preponderance (11 : 20).…”

Is it time for a change? The case for early application of unrelated allo-SCT for severe aplastic anemia

“…This recommendation is based on the findings from numerous groups of excellent short-term and long-term outcomes in patients treated with this approach. [2][3][4][5][6][7][8] In patients aged 50-60 years with a matched sibling donor, up front transplantation should be strongly considered in the context of other comorbidities and complications. The major toxicities from allogeneic BMT that impact outcome include engraftment failure, infectious complications and GVHD.…”

“…With the use of irradiated blood products and avoidance of blood products from family members in the pretransplant period, engraftment failure rates have dropped significantly, with current rates under 10%. [2][3][4][5][6][7][8] Outcomes of infectious complications are also improving with the expansion of antibacterial and antifungal therapies and preemptive treatment of CMV infection and disease. GVHD remains to be the major factor impacting outcomes of matched related donor transplantation for SAA.…”