[evansmom]

Evan had horse ATG, 5 doses over 5 days, followed by prednisone and cyclosporin. The prednisone was tapered out after a month or so and the cyclo, of course, continued up to transplant. In the month after diagnosis and before the ATG, Evan did not need transfusions. His hgb stayed around 80 and his platelets around 20. ANC was around 0.6. In the weeks that followed ATG, Evan was his most transfusion dependent. He needed platelets every 4 days or so and red cells every 2 weeks. Around 2 months post ATG, Evan settled out again and stayed low but stable without transfusions. He went back to school with hgb 85, platelets 25, ANC 1.2. Then in March 2008, 4 months post ATG, his counts plummeted: hgb 64, platelets 8, ANC 0.3. From that point, he needed very frequent transfusions. He was back out of school and we were talking transplant. On a side note, looking back, I believe the reason for his counts tanking was because cyclosporin was causing damage to his tiny blood vessels, causing his red cells to break apart, not because of advancing or worsening AA. I believe this because post BMT, Evan had a similar reaction to tacrolimus, a sister to cyclosporin in the class of calcineurin inhibitors, which caused a very serious drop in hgb i.e. from 84 to 48 in 3 days. While the clinic thought this was OK, I knew it was not. Pushing for investigations, we came to realize this rare and serious side effect (microangiopathy). Once we switched him to a different class of immunosuppressant (MMF), he recovered rather quickly and never looked back from there. Word of advice as far as this point is concerned: if at any point your son's hgb starts dropping uncharacteristically, suspect microangiopathy and ask questions. Diagnosis is confirmed by red cell fragments or schistocytes on the smear, low haptoglobin and very high LDH. The urine will be tea or rusty coloured. I tell you this because it is rare and rare = many doctors not recognizing it until damage is done or patient's condition becomes serious.
I sometimes wonder if we had recognized this condition happening before BMT and switched meds, that maybe Evan would have been a responder to ATG. I'll never know, I'm just so thankful that it all worked out alright.

We were given the option of a second round of ATG (rabbit) or doing the BMT provided the potential donors were still available. By this point, I had already read studies that indicated that AA kids have better outcomes if after 6 months of no response to ATG, BMT is done (again provided suitable donor available) versus doing ATG again. For us, it was an easy choice because we never saw his counts climb. There was no response. So in our minds we thought if one round of ATG didn't work, why would we believe a second round would work? Maybe it would...but maybe it wouldn't. We had a donor ready and willing and we didn't want to waste precious time trying something that may not work, especially knowing more immunosuppression therapy and more transfusions = more potential complications in BMT.

Prospective multicenter trial comparing repeated immunosuppressive therapy with stem-cell transplantation from an alternative donor as second-line treatment for children with severe and very severe aplastic anemia.

Kosaka, Yoshiyuki. Yagasaki, Hiroshi. Sano, Kimihiko. Kobayashi, Ryoji. Ayukawa, Hiroshi. Kaneko, Takashi. Yabe, Hiromasa. Tsuchida, Masahiro. Mugishima, Hideo. Ohara, Akira. Morimoto, Akira. Otsuka, Yo****oshi. Ohga, Shouichi. Bessho, Fumio. Nakahata, Tatsutoshi. Tsukimoto, Ichiro. Kojima, Seiji. Japan Childhood Aplastic Anemia Study Group.


Blood. 111(3):1054-9, 2008 Feb 1


We conducted a prospective multicenter study to compare the efficacy of repeated immunosuppressive therapy (IST) with stem-cell transplantation (SCT) from an alternative donor in children with acquired aplastic anemia (AA) who failed to respond to an initial course of IST.

Patients with severe (n = 86) and very severe disease (n = 119) received initial IST consisting of antithymocyte globulin (ATG) and cyclosporine. Sixty patients failed to respond to IST after 6 months from the initial IST and were eligible for second-line treatment.

Among them, 21 patients lacking suitable donors received a second course of IST. Three patients developed an anaphylactoid reaction to ATG and could not complete the second IST.

A trilineage response was seen in only 2 of 18 (11%) evaluable patients after 6 months.

Thirty-one patients received SCT from an alternative donor.

At 5 years from the initiation of second-line therapy, the estimated failure-free survival (FFS), defined as survival with response, was 83.9% (+/- 16.1%, SD) in the SCT group compared with 9.5% (+/- 9.0%) in the IST group (P = .001).

These results suggest that SCT from an alternative donor offers a better chance of FFS than a second IST in patients not responding to an initial IST.

Arm yourself with as much information as possible, you have involuntarily enrolled in a Bone Marrow 101 rapid study course.