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Comment on: Consolidation treatment for high risk solid tumors in children with myeloablative chemotherapy and autologous hematopoietic progenitor stem cell transplantationConsolidation treatment for high risk solid tumors in children with myeloablative chemotherapy and autologous hematopoietic progenitor stem cell transplantation

This paper reports on a small number of patients with a diverse group of diagnoses that were consolidated with high-dose therapy and rescued with autologous hematopoietic progenitor cells (HPC)(11. Vargas AO, Luna RR, Garcia MP, Cardos RC, Hidalgo LV, Jácome DL, et al. Consolidation treatment for high risk solid tumors in children with myeloablative chemotherapy and autologous hematopoietic progenitor stem cell transplantation. Rev Bras Hematol Hemoter. 2013;35(5):343-8.). One of the problems with this manuscript and many others is that the studies that have been performed and reported in the literature only reflect those patients who get the rescue and the survival advantage is from that point on. Second the number of patients is small and conclusions about the effectiveness of the procedure are not reliable. The only exception to these two problems has been the report of the only randomized trial for patients with high-risk neuroblastoma that actually includes all patients from diagnosis and shows a slight benefit of autologous hematopoietic stem cell rescue vs. conventional therapy(22. Matthay KK, Reynolds CP, Seeger RC, Shimada H, Adkins ES, Hass-Kogan D, et al. Long term results for children with high risk neuroblastoma treated won a randomized trial of myeloablative therapy followed by 13-cis retinoic acid: a children's oncology group study. J Clin Oncol. 2009;27(7):1007-13.). Does that mean that autologous hematopoietic stem cell rescue is not an effective therapy. My response is that maybe an effective consolidation therapy in a selected group of patients with certain diagnoses. For example, in patients with recurrent Wilms tumors who achieve a second complete remission and are consolidated with high-dose therapy and autologous HPC do very well(33. Campbell AD, Cohn SL, Reynolds M, Seshadri R, Morgan E, Geissler G, et al. Treatment of relapsed Wilms tumor with high dose therapy and autologous hematopoietic stem cell rescue, the experience at Children's Memorial Hospital. J Clin Oncol. 2004;22(14):2885-90.

4. Agarwal R, Dvorak CC, Stockerl-Goldstein KE, Johnston L, Srinivas S. Highdose chemotherapy followed by stem cell rescue for highrisk germ cell tumors: the Stanford experience. Bone Marrow Transplant. 2009;43(7):547-52.

5. Burke MJ, Walterhouse DO, Jacobsohn DA, Duerst RE, Kletzel M. Tandem highdose chemotherapy with autologous peripheral hematopoietic progenitor cell rescue as consolidation therapy for patients with highrisk Ewing family tumors. Pediatr Blood Cancer. 2007;49(2):196-8. Comment in: Pediatr Blood Cancer. 2007;49(2):115-6.
-66. Fraser CJ, Weigel BJ, Perentesis JP, Dusenbery KE, DeFor TE, Baker KS, et al. Autologous stem cell transplantation for highrisk Ewing's sarcoma and other pediatric solid tumors. Bone Marrow Transplant. 2006;37(2):175-81.) unfortunately the reports about the benefit are with multiple different conditioning regimens some with a single rescue and others with a double rescue where deciding what is the standard to which we can compare results is not available. Other reports have shown that the survival in the same group of patients maybe equally as good without HPC rescue(77. Presson A, Moore TB, Kempert P. Efficacy of high dose chemotherapy and autologous stem cell transplant for recurrent wilms tumor: a metanalysis. J Pediatr Hematol Oncol. 2010;32(6):454-61).

Maybe we have to start thinking differently about the use of autologous HPC transplants. These transplants are no more than the use of HPC to recover patients from the effects of myeloablative therapy and so the use of multiple cycles of high-dose therapy with an intensification of the therapy to overcome tumor resistance to chemotherapy may be feasible. In fact, there are examples in the literature where this approach has been used in neuroblastoma(88. Kletzel M, Katzenstein HM, Haut PR, Yu AL, Morgan E, Reynolds M, et al. Treatment of high risk neuroblastoma with triple tandem high dose therapy and stem cell rescue: results of the Chicago pilot II Study. J Clin Oncol. 2002;20(9):2284-92.,99. George RE, Li S, Medeiros-Nancarrow C, Neuberg D, Marcus K, Shamberger RC, et al. High risk neuroblastoma treated with tandem autologous peripheral blood stem cell supported transplantation: long term survival update. J Clin Oncol. 2006;24(18):2891-6.), and brain tumors (1010. Sung KW, Lim Do H, Son MH, Lee SH, Yoo KH, Kim JH, et al. Reduced-dose craneospinal radiotherapy followed by tandem high dose chemotherapy and autologous stem cell transplantation in patients with high risk medulloblastoma. Neuro Oncol. 2013;15(3):352-9.,1111. Gilman AL, Jacobsen C, Bunin N, Levine J, Goldman F, Bendel A, et al. Phase I study of tandem high-dose chemotherapy with autologous peripheral stem cell rescue for children with recurrent brain tumors: a pediatric blood and marrow transplant Consortium study. Pediatr Blood Cancer. 2011;57(3):506-13.).

In my view the only way we will be able to determine the true effect of autologous HPC in the treatment of cancer is by performing randomize trials comparing the standard therapy to the use of high-dose therapy with HPC rescue. The reasons that these studies will be difficult to do are: the small number of patients with this type of diagnosis for a randomized trial and how to determine which conditioning regimen is the best. An example could be Wilms tumor which is mostly curable with standard therapy; the number of relapse patients is small and diverse with respect to the site of relapse and the length of the initial response. Then we have to take into consideration what therapy they received for their initial treatment, how much radiation they received and lastly what chemotherapy, surgery or radiation will be given to induce them into a second remission. By the time we accumulate some patients, the results will be difficult to interpret and to make meaningful conclusions. In our own institution in a report by Campbell et al.(33. Campbell AD, Cohn SL, Reynolds M, Seshadri R, Morgan E, Geissler G, et al. Treatment of relapsed Wilms tumor with high dose therapy and autologous hematopoietic stem cell rescue, the experience at Children's Memorial Hospital. J Clin Oncol. 2004;22(14):2885-90.), it took almost 10 years to collect enough patients to report the results.

One last question is whether we should use this approach in the up front therapy as was used in the neuroblastoma study for patients at very high risk of relapse and my response is that it would be an ideal approach to determine whether high dose therapy with HPC rescue has value for each one of the diseases for which this approach was used in this report.

In conclusion, autologous HPC rescue is a safe procedure but we can only conclude that it provides benefits in patients with high-risk neuroblastoma and that further studies with a large group of patients and preferably in a randomized trial with an upfront approach in high-risk patients will be necessary to arrive at the conclusions that Vargas et al. made in this report(11. Vargas AO, Luna RR, Garcia MP, Cardos RC, Hidalgo LV, Jácome DL, et al. Consolidation treatment for high risk solid tumors in children with myeloablative chemotherapy and autologous hematopoietic progenitor stem cell transplantation. Rev Bras Hematol Hemoter. 2013;35(5):343-8.).

References

  • 1
    Vargas AO, Luna RR, Garcia MP, Cardos RC, Hidalgo LV, Jácome DL, et al. Consolidation treatment for high risk solid tumors in children with myeloablative chemotherapy and autologous hematopoietic progenitor stem cell transplantation. Rev Bras Hematol Hemoter. 2013;35(5):343-8.
  • 2
    Matthay KK, Reynolds CP, Seeger RC, Shimada H, Adkins ES, Hass-Kogan D, et al. Long term results for children with high risk neuroblastoma treated won a randomized trial of myeloablative therapy followed by 13-cis retinoic acid: a children's oncology group study. J Clin Oncol. 2009;27(7):1007-13.
  • 3
    Campbell AD, Cohn SL, Reynolds M, Seshadri R, Morgan E, Geissler G, et al. Treatment of relapsed Wilms tumor with high dose therapy and autologous hematopoietic stem cell rescue, the experience at Children's Memorial Hospital. J Clin Oncol. 2004;22(14):2885-90.
  • 4
    Agarwal R, Dvorak CC, Stockerl-Goldstein KE, Johnston L, Srinivas S. Highdose chemotherapy followed by stem cell rescue for highrisk germ cell tumors: the Stanford experience. Bone Marrow Transplant. 2009;43(7):547-52.
  • 5
    Burke MJ, Walterhouse DO, Jacobsohn DA, Duerst RE, Kletzel M. Tandem highdose chemotherapy with autologous peripheral hematopoietic progenitor cell rescue as consolidation therapy for patients with highrisk Ewing family tumors. Pediatr Blood Cancer. 2007;49(2):196-8. Comment in: Pediatr Blood Cancer. 2007;49(2):115-6.
  • 6
    Fraser CJ, Weigel BJ, Perentesis JP, Dusenbery KE, DeFor TE, Baker KS, et al. Autologous stem cell transplantation for highrisk Ewing's sarcoma and other pediatric solid tumors. Bone Marrow Transplant. 2006;37(2):175-81.
  • 7
    Presson A, Moore TB, Kempert P. Efficacy of high dose chemotherapy and autologous stem cell transplant for recurrent wilms tumor: a metanalysis. J Pediatr Hematol Oncol. 2010;32(6):454-61
  • 8
    Kletzel M, Katzenstein HM, Haut PR, Yu AL, Morgan E, Reynolds M, et al. Treatment of high risk neuroblastoma with triple tandem high dose therapy and stem cell rescue: results of the Chicago pilot II Study. J Clin Oncol. 2002;20(9):2284-92.
  • 9
    George RE, Li S, Medeiros-Nancarrow C, Neuberg D, Marcus K, Shamberger RC, et al. High risk neuroblastoma treated with tandem autologous peripheral blood stem cell supported transplantation: long term survival update. J Clin Oncol. 2006;24(18):2891-6.
  • 10
    Sung KW, Lim Do H, Son MH, Lee SH, Yoo KH, Kim JH, et al. Reduced-dose craneospinal radiotherapy followed by tandem high dose chemotherapy and autologous stem cell transplantation in patients with high risk medulloblastoma. Neuro Oncol. 2013;15(3):352-9.
  • 11
    Gilman AL, Jacobsen C, Bunin N, Levine J, Goldman F, Bendel A, et al. Phase I study of tandem high-dose chemotherapy with autologous peripheral stem cell rescue for children with recurrent brain tumors: a pediatric blood and marrow transplant Consortium study. Pediatr Blood Cancer. 2011;57(3):506-13.

Publication Dates

  • Publication in this collection
    2013

History

  • Received
    05 Aug 2013
  • Accepted
    12 Aug 2013
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