Allogeneic peripheral blood stem cell transplantation using a fludarabine-based low intensity conditioning regimen for malignant lymphoma

Abstract

Summary:Relapse is a serious complication following high-dose therapy and autologous bone marrow transplantation (ABMT) for malignant lymphoma (ML). Allogeneic transplantation (alloSCT) is a therapeutic option. However, it is associated with a high incidence of transplantrelated organ toxicity and mortality. We recently reported fast engraftment and minimal transplantrelated toxicity, using fludarabine-based conditioning with reduced amounts of chemotoxic drugs prior to alloSCT. We now present our experience with 23 heavily treated high risk ML patients who underwent matched alloSCT following the same low intensity conditioning. The patients (20 male, three female) were aged 13-63 years. Nineteen had NHL and four HD (resistant disease 12, partial remission 11). Five were post ABMT. Twenty-two patients had fully matched sibling donors, and one a fully matched unrelated donor. Engraftment was fast. There was no rejection or nonengraftment. Organ toxicity was moderate with no liver or renal toxicity Ͼgrade II. Four patients developed Ͼgrade II graft-versus-host disease (GVHD). Seven patients died -four of grade III-IV GVHD and severe infections, two of bacterial sepsis, one of pulmonary failure. Ten patients are alive after 22.5 (15-37) months. Survival and disease-free survival at 37 months are both 40%. Probability of relapse is 26%. These encouraging results suggest that alloSCT following fludarabinebased low intensity conditioning in high-risk patients merits further evaluation. Bone Marrow Transplantation (2000) 25, 1021-1028. Keywords: allogeneic; peripheral blood stem cell transplantation; malignant lymphoma; fludarabine; low intensity conditioning regimen High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT) has gained widespread acceptance as the treatment for aggressive nonHodgkin's lymphoma (NHL) in chemosensitive relapse,

Fludarabine and treosulfan compared with other reduced-intensity conditioning regimens for allogeneic stem cell transplantation in patients with lymphoid malignancies

“…23,24 NRM is lower after RIC, in the range of 20-35%, which is still higher than NRM after RIC in AML/myelodysplastic syndromes. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] This is possibly related to patients with lymphoma been older and more heavily treated at the time of SCT including a high incidence of prior autologous SCT. In the current study NRM was relatively low after FT and FB2, both 24%, similar to RIC regimens, whereas it was 54% after FM which is more similar to MAC regimens.…”

“…Survival rates in the range of 20-52% have been reported in other, smaller studies depending on patient characteristics at SCT. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Chemo-refractory disease is the most important predicting factor for survival across all studies. However, a small subset of patients with refractory lymphoma can achieve long-term survival with allogeneic SCT with both MAC and RIC.…”

“…Reduced intensity (RIC) and nonmyeloablative (NMA) conditioning regimens have allowed marked reduction in NRM and extension of the indications and patient groups able to tolerate treatment. [11][12][13][14][15][16][17] More than two thirds of patients with lymphoid malignancies are currently offered these regimens. 18 Although patients with myeloid malignancies are often selected for RIC based on age, comorbidities and disease status, 19 patients with lymphoid malignancies are often selected for RIC based on the disease type alone.…”

Treosulfan-based conditioning before hematopoietic SCT: more than a BU look-alike

“…45 Certain toxic side effects reported after RIC were less prevalent in treosulfan-based transplants or did not occur in these patients. Although reduced-dose combinations with BU may still lead to severe hepatic toxicity 51 or to VOD, 39,52 the liver toxicity (alanine transaminase/aspartate aminotransferase elevation) seen with treosulfan was transient and did not exceed grade III. 40 No VOD occurred in the patients treated with treosulfan.…”

The role of allogeneic haematopoietic progenitor cell transplantation in patients with diffuse large B-cell non-Hodgkin lymphomas (DLBCL)

“…This allowed the extension of allo-HCT to older patients or those with comorbidities and patients whose disease had progressed or relapsed after auto-HCT. 30,31 Although an early EBMT registry study reported disappointing outcomes for patients with high-grade NHL who underwent RIC allo-HCT with high rates of relapse (79% at 2 years), 32 recent trials in DLBCL have demonstrated the efficacy of this approach mainly in patients with chemosensitive disease 23,28,[32][33][34][35][36] (Table 2).…”