Transplantation in adult ALL

Abstract

The value of the allogeneic graft-versus-leukemia effect in adult acute lymphoblastic leukemia (ALL) has now been conclusively demonstrated and confirmed. While this is true for adults in all age groups, it may not be the best clinical option for young adults for whom increasingly intensive pediatric protocols are clearly of benefit. On the other hand, there is potentially wider applicability of allogeneic donor transplantation for adults 25 to 45 years old, for whom matched unrelated donors may be as safe and effective as sibling donors, and for the patient older than 45 years for whom reduced-intensity conditioning may be a promising way forward.Since the treatment-related mortality of allogeneic transplantation remains significant, careful selection of patients is mandatory. Patients with the Philadelphia chromosome, those with t(4;11) and those with a complex karyotype remain transplant candidates, and allogeneic transplantation remains the best option for salvage, where achievable, in a remission beyond first.As in childhood ALL minimal residual disease studies may be extremely useful in predicting outcome and, therefore, strategy, but at present there are less definite data in adults. Clinical indications to harness the allogeneic effect will mature as the true value of pediatric protocols in adult patients and the safety and efficacy of a sibling, unrelated and reduced intensity transplant emerge in this disease.

Non-myeloablative conditioning with allogeneic hematopoietic cell transplantation for the treatment of high-risk acute lymphoblastic leukemia

“…2,32 Developing HCT approaches for older or medically infirm patients with ALL has remained challenging. While the outcome for patients not undergoing allogeneic HCT is very poor, those who proceed with myeloablative conditioning followed by HCT have an unacceptably high rate of non-relapse mortality.…”

A prospective randomized trial comparing cyclosporine/methotrexate and tacrolimus/sirolimus as graft-versus-host disease prophylaxis after allogeneic hematopoietic stem cell transplantation

“…[1][2][3] Continuous refinements of transplant procedures, e.g. in the areas of human leukocyte antigen (HLA)-typing, expanded donor registries, conditioning regimens and supportive care, have steadily improved patient outcome after HSCT.…”

High curability via intensive reinduction chemotherapy and stem cell transplantation in young adults with relapsed acute lymphoblastic leukemia in Sweden 2003-2007

“…High-risk ALL was defined by the presence of at least one of the following criteria: white blood cell (WBC) count >30×10 9 /L (>100×10 9 /L for T-ALL), central nervous system disease, more than one course required to achieve CR1, Philadelphia-positive chromosome-positive or t(4;11), and for patients first diagnosed in 2003-2007, high levels of minimal residual disease (>1% after induction or >0.1% after consolidation). Myeloablative allogeneic SCT in CR1 was recommended for these patients but not for patients with standard-risk ALL.…”

“…This age group is considered as high-risk both at diagnosis 7,8 and relapse. 9 Prognosis remains very poor for relapsing patients, with approximately 40% achieving second complete remission (CR2) through salvage regimens and only 7-12% becoming long-term survivors. [10][11][12] Allogeneic SCT seems to be the best consolidation option for adult patients with relapsed ALL, [10][11][12] although only a minority of such patients are eligible for the procedure as a result of poor performance status, lack of a donor or short duration of CR2.…”