Cancer Treatment Today

A 2000 TEC assessment focused on high-dose chemotherapy and allogeneic stem cell support after a prior failed course of high-dose chemotherapy and autologous stem cell support, in the treatment of a variety of malignancies, including AML. The TEC Assessment found insufficient data to permit conclusions about this treatment strategy. A small series of pediatric patients (n=23) treated in this fashion has been published since that Assessment. The study reports nine of twenty-one AML patients surviving after HDC/AlloSCS, but also reports an equal proportion of deaths from regimen-related toxicity. Autologous transplantation, however, is out of fashion for AML.

A mini-review on second allogeneic transplant found that a second allogeneic hematopoietic cell transplant does have an important potential role in treating relapse after failing allogeneic transplant in selected patients. Those patients who have an early relapse, high tumor burden, or chemo-resistant disease are not patients who should undergo second transplant, as the literature does not support the clinical benefit for these selected patients. Thus the decision to undergo a second transplant should be weighed against the associated co-morbidities that can contribute to transplant-related mortality, for which a reduced-intensity approach can certainly be considered, with earlier tapering of immunosuppression. With regard to the donor, under most circumstances the same donor is used, but if there is a different HLA-matched sibling or unrelated donor, this also could be considered, especially if there was no antecedent GVHD. As randomized-controlled trials are non-existent to answer the question of the role of second allogeneic transplant to treat relapse, multi-institutional observational studies were used in this mini-review to make these recommendations.

Literature supports individualizing recommendations. A short interval to relapse is a factor that speaks against repeating an allogeneic transplant. A recent review wrote: ” The prognosis for relapsed hematological malignancies after SCT depends on four factors: the time elapsed from SCT to relapse (with relapses occurring within 6 months having the worst prognosis), the disease type (with chronic leukemias and some lymphomas having a second possibility of cure with further treatment), the disease burden and site of relapse (with better treatment success if disease is treated early), and the conditions of the first transplant (with superior outcome for patients where there is an opportunity to increase either the alloimmune effect, the specificity of the antileukemia effect with targeted agents or the intensity of the conditioning in a second transplant). These features direct treatments toward either modified second transplants, chemotherapy, targeted antileukemia therapy, immunotherapy or palliative care.”

Transplantation for consolidation of high-risk is standard of care. AML Literature supports individualizing recommendations. A short interval to relapse is a factor that speaks against repeating an allogeneic transplant. A recent review wrote: ” The prognosis for relapsed hematological malignancies after SCT depends on four factors: the time elapsed from SCT to relapse (with relapses occurring within 6 months having the worst prognosis), the disease type (with chronic leukemias and some lymphomas having a second possibility of cure with further treatment), the disease burden and site of relapse (with better treatment success if disease is treated early), and the conditions of the first transplant (with superior outcome for patients where there is an opportunity to increase either the alloimmune effect, the specificity of the antileukemia effect with targeted agents or the intensity of the conditioning in a second transplant). These features direct treatments toward either modified second transplants, chemotherapy, targeted antileukemia therapy, immunotherapy or palliative care.”

Recently mismatched unrelated transplants have come to fore. The conclusions of a 2012 ASH review were that patient factors such as phase of the disease remain critical predictors of survival: when the disease is advanced, identifying a fully matched donor may not improve survival significantly and must be balanced against the risk that the disease will progress while a prolonged search is ongoing.
The recent review by SWaraceni et al concluded that : ” that in AML patients in CR1 lacking an HLA-matched sibling donor, 10/10 UD-HSCT significantly improves LFS, but this advantage does not translate in better OS compared to auto-HSCT. In intermediate-risk patients lacking a fully HLA-matched donor, auto-HSCT should be considered as a valid option, as better survival appears to be provided by auto-HSCT compared to mismatched UD-HSCT. Finally, auto-HSCT provided an encouraging outcome in patients with favorable risk AML.:
Saraceni F, Labopin M, Gorin NC, et al. Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT. J Hematol Oncol. 2016;9(1):79.

Hosing C, Saliba RM, Shahjahan M, Estey EH, Couriel D, Giralt S, et al. Disease burden may identify patients more likely to benefit from second allogeneic hematopoietic stem cell transplantation to treat relapsed acute myelogenous leukemia. Bone Marrow Transplant. 2005;36:157-62.

M. S. Thakar and S. J. Forman ASH evidence-based guidelines: is there a role for second allogeneic transplant after relapse? Hematology, January 1, 2009; 2009(1): 414 – 418.

nccn.org, AML 2018, AML-14

Barrett, A John; Battiwalla, Minoo Relapse after allogeneic stem cell transplantation Expert Review of Hematology, Volume 3, Number 4, August 2010 , pp. 429-441(13)