Adam's Story (11)
After high-dose there was the inevitable period during which Adam was dependent on blood and platelet transfusions whilst his fragile bone marrow began to function. At first we would be up at our local hospital every other day for platelets, then every three or four days, and then less frequently still. By the start of April his counts were holding up on their own, and whilst nowhere near normal it meant the seemingly endless cycle of platelet transfusion after platelet transfusion was finally broken. A full set of diagnostic tests following high-dose - CT, MIBG and bone marrow biopsies showed continued stable disease, no better, no worse. In spite of everything we had thrown at Adam's disease the best indicators for neuroblastoma still showed it to be widespread within him.
Deciding what to do next was even more difficult than deciding whether or not to press ahead with high-dose and transplant. Knowing that Adam's original diagnosis was differentiating neuroblastoma, and his extended period of stable disease was suggestive of more mature, less aggressive, neuroblastoma, we started retinoid therapy in May 2011. Fourteen days of oral 13-cis-retinoic acid, followed by a fourteen day break. This therapy has been demonstrated to induce maturation (differentation) of malignant neuroblastoma cells into non-malignant cells, and thus prevent relapse.
We looked at further options for continuing treatment, but the lack of proven active disease was a problem. Whilst MIBG positivity showed that something was there it didn't, particularly after all the treatment Adam had received, tell us precisely what it was. And for clinical trials that aim to show objective responses (or otherwise) to treatment, having something that might not be active disease is a problem. If it's inactive then it doesn't matter what you treat it with you won't see any changes, so you add nothing to a trial by including such patients on it. We considered ch14.18 + IL2 antibody therapy in Greifswald, Germany where we knew other UK children had gone for treatment. We also researched a newly opening Phase III trial in America that combined hu14.18-IL2 immunocytokine with GM-CSF and isotretinon (13-cis-RA).
Considering published results from Phase I and II trials of the hu14.18-IL2 fusion protein, and the lack of data from Germany we decided America would be the best option. The problem was without a biopsy as evidence of active disease Adam was ineligible for the trial. The Marsden conducted a series of additional investigations to try and gather as much information as possible; we did (18)F-FDG PET/CT which was clear, Gallium Octreotide which showed a small amount of abnormal uptake in the right femur, and MRI of the right pelvis and femur which came back clear. The only things we were able to conclude from all this were that it wasn't possible to conclude anything, and there was nothing biopsiable that would get us a place on the American trial. It was either Germany, or it was no antibody therapy.
If I took convincing about the merits of high-dose in Adam's case then I took as much, if not more convincing, about antibodies. I couldn't get hold of any quantitative data and I knew of a number of children who had been to Germany and either progressed on treatment or relapsed once they returned. I was told be expert after expert that this was the right thing to do. That Adam might not need antibodies, but the chances of him being cured would be improved by him having them. And in the end I agreed. I think the truth is I was too scared of saying no and being wrong. My reservations were genuine but either they weren't strong enough, or I wasn't brave enough to act upon them.