Allogeneic Hematopoietic Stem Cell Transplantation in Adolescent and Adult Patients with High-Risk T Cell Acute Lymphoblastic Leukemia

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is often recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission ($CR2) and sometimes in high-risk (HR) patients in first complete remission (CR1). Between January 1995 and July 2009, 53 patients with HR TALL underwent allo-SCT at our institution. Median age was 18 years (range, 14-51). Thirty-two patients (60.3%) were in CR1, 18 (34%) were in $CR2, and 3 (5.7%) were in relapse. The cumulative incidence of nonrelapse mortality at 5 years was 22.5%. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 40.2%, and that of chronic GVHD was 43.7%. The majority of relapses (88.9%) occurred within 1 year after SCT. The cumulative incidence of relapse (CIR) at 5 years was 35.6%. CIR was 29.8% in patients in CR1, 35.3% in patients in $CR2 and all patients transplanted in relapse had disease recurrence post-allo-SCT (P 5 .000). Overall survival (OS) and disease-free survival (DFS) at 5 years were 43.5% and 41.8%, respectively. The 5-year OS was 53.5% (95% CI 34.5%-72.5%) and 5-year DFS was 52% (95% CI 33%-71%) in patients who underwent allo-SCT in CR1, compared with 31.9% (95% CI, 9%-54.8%) and 29.4% (95% CI 7.6%-51.2%) in those who underwent allo-SCT in $CR2. On multivariate analysis, disease status at SCTremained significantly associated with OS (P 5.007), DFS (P 5.002), and CIR (P 5.000). The presence of extramedullary disease at diagnosis had no effect on the different outcomes. Grade II-IV acute GVHD was significantly associated with a lower OS (P 5.006) and DFS (P 5.01). Our data indicate that allo-SCTrepresents an effective treatment for HR TALL , particularly when performed in CR1.

Allogeneic Hematopoietic Cell Transplantation for Adult T Cell Acute Lymphoblastic Leukemia

“…These data also identify disease status at transplantation as the most important risk factor for survival, confirming previous studies demonstrating the prognostic significance of achieving CR at the time of transplantation [4–6]. A single-institution study evaluated 53 patients with high risk T-ALL who underwent allogeneic HCT [4]. High risk was defined as patients in CR2+ or relapse or those in CR1 who were age ≥35 years, had a WBC count at presentation of ≥100,000/mm 3 , had residual disease in the bone marrow at day 15 postinduction, had CNS involvement at diagnosis, had high-risk cytogenetic features, and/or required more than 1 induction regimen to achieve CR1.…”

“…In our large contemporary cohort of T-ALL patients undergoing allogeneic HCT, including recipients of an RIC regimen and alternative donor HCT, one-third of the patients with high-risk disease survived for more than 5 years; however, relapse was the major cause of treatment failure. These data also identify disease status at transplantation as the most important risk factor for survival, confirming previous studies demonstrating the prognostic significance of achieving CR at the time of transplantation [4–6]. A single-institution study evaluated 53 patients with high risk T-ALL who underwent allogeneic HCT [4].…”

“…Allogeneic hematopoietic cell transplantation (HCT) is typically recommended for adults with T-ALL in second or later complete remission (CR2+), but also may be offered to patients in first CR (CR1) with high-risk features. There have been few reports on allogeneic HCT for the treatment of T-ALL [4–6]. In a prospective cohort of 356 adults with T-ALL treated uniformly between 1993 and 2006 on the Medical Research Council UKALL XII/Eastern Cooperative Oncology Group 2993, a donor/no-donor comparison demonstrated superior 5-year survival in patients with matched sibling donors compared with those without donors (61% versus 46%; P = .02), as a result of less relapse (25% versus 51% at 5 years; P < .001) [1].…”

Impact of conditioning with TBI in adult patients with T-cell ALL who receive a myeloablative allogeneic stem cell transplantation: a report from the acute leukemia working party of EBMT

“…10 Few allo-SCT data specific to adult T-ALL have been described. 2,7,11 As T-ALL patients are usually young with a median age of ∼ 30 years, they often display few comorbidities and are eligible for myeloablative allo-SCT. 2 Whenever the indication to proceed to allo-SCT has been decided, physicians can choose among various conditioning regimens from TBI-based regimens such as TBI-cyclophosphamide (Cy) to chemotherapy-based regimens such as IV busulfan (Bu)-Cy.…”

Transplant Outcomes for Children with T Cell Acute Lymphoblastic Leukemia in Second Remission: A Report from the Center for International Blood and Marrow Transplant Research

“…14, 15 Reported outcomes have generally been poor with predicted EFS <20% with either HCT or chemotherapy alone approaches. 14–16 Past analyses included older treatment eras (1980s and 1990s) with little data on current HCT outcomes for children with relapsed T-ALL receiving contemporary treatment strategies. Whether improvements in the current HCT era (post-2000) have resulted in improved survival, particularly with enhanced high-resolution HLA-typing 17 and better supportive care 18 , is unclear.…”