| These notes are from the meeting at Camp Sunshine in July 2006. Please consult a physician for any medical advice Outcomes of Remission: 61 patients in the DBAR have sustained remission (more than 6 months without treatment). 44 remitted from steroid therapy, 10 from transfusion therapy, 2 with no treatment, 5 unknown. 9 patients relapsed (2 later remitted and 1 died from complications of SCT). The actuarial likelihood of remission is 20% by age 25, with 72% of those happening during the first decade of life. In the DBAR, there are 44 patients to remitted prior to age 10, 15 after age 10, and 2 unknown. The conclusion regarding remission out comes is that although there seems to be equal numbers (proportionally) remitting from either steroid or transfusion therapy, only 2 of the patients remitting from transfusion had failed steroid therapy (1 primary and 1 secondary failure). Steroids do not seem to induce remission (4 remitters were never treated with steroids). [Pregnancy hormones seem to really knock women out of remission and usually go right back into it after deliver. Birth control pills or other estrogen supplements can knock you out of remission. Often as girls enter puberty they will be knocked out of remission.] [One thing to note, and I can't remember if it was this talk or one on steroids, that Dr. L and V said there's no evidence that when a steroid responder goes off steroids for a steroid holiday that they have a chance of not responding.] Outcomes of Stem Cell Transplantation: There are 36 patients in the DBA with transplants, all done since 1993. There are 28 bone marrow, 1 peripheral blood, 6 umbilical cord, and 1 UCB/BM combo. 21 had a sibling or matched relative (I think that's 20 sibling, 1 matched relative). 15 had an alternative donor. 2 of those 15 had mismatched related donors, and 13 had unrelated donors. Of the 20 HLA matched sibling or the 1 other related donor, 20 were transfusion dependent or steroid intolerant. One had aplastic anemia. Of the 15 with alternative donors, 12 were transfusion dependent or steroid intolerant. 1 had thrombocytopenia and steroid intolerance. One had aplastic anemia and one had AML. There have been 3 patients with a non-myeloablative SCTs reported to the DBAR [this is the "mini" transplant]. These patients are a 32 year old male, a 5 year old female, and an 8 year old female. All were transfusion dependent. The stem cell sources were (in order) unrelated BM, related UCB, and related BM. In the DBAR, for patients with transplants, 20 are alive, 16 have died. 16 of the 21 allogeneic related transplants are alive, none of the 2 mismatched related are alive, and 4 of the 13 related are alive. Causes of death are infection, VOD [can't remember what this acronym is, but this is where the liver can't handle the chemo], GvHD [graft vs. host, where the new white cells attack the patient's body], and only one death from primary graft failure [where the bone marrow fails to start working in the patient]. Actuarial survival rates for SCT are 72.7+/-10.7% for allogenaic sibling donors (note that if the patient is under 10 years old, this rises to 92.3+/-7.7%). For an alternative donor, the chances of survival are only 19.1 +/- 11.9%. The conclusions from the SCT study are: DBA patients with HLA-identical matched siblings should be considered early for SCT. Alternative donor SCT should be considered on a case-by-case basis. [I believe this was in her SCT talk not this one, but Dr. Vlachos said that the "mini" transplant is ONLY an option for those who, for some reason, cannot do a regular transplant - some sort of liver misfunction, diabetes, etc. A mini carries a whole host of other risks. The mini leaves some host cells, which are more susceptible to AML, and also could in the future take over/consume the donor cells and leave the patient with DBA again.] SCT Controversies and Cautions: Likelihood of durable remission [a positive]. Likelihood of SAA/MDS/AML [bad, but less than 1% chance]. Likelihood of donor with a silent phenotype resulting in graft failure [meaning the donor "carries" DBA but doesn't have symptoms, in which case the marrow won't "take"]. Higher than expect mortality? [this is questionable b/c there aren't enough patients to give a statistical sample, plus the survivability is so dependent on age, health, transplant type] Implications of gene therapy [meaning that hopefully in the future they'll be able to take the patient's own marrow, do gene therapy on it to fix the genes, and transplant it back]. [If you develop aplastic anemia after having DBA you HAVE to have a transplant. Regular aplastic anemia patients can use alternative therapies, but they don't work for DBA.] OK, this section of overheads is back to the DBAR as a whole, regardless of treatment: Outcomes: There are 36 deaths reported in the DBAR. 25 (70%) of them are treatment related: 5 from infections (2 PCP. 1 varicella pneumonia, 1 Pseudomonas pneumonia/sepsis, 1 unknown);1 from vascular access device [port/cath] complication; 5 from complications of iron overload; 14 from stem cell transplant related complications. 8 deaths are DBA related (22%): 1 from severe aplastic anemia, 7 from a malignancy (2 of those post-SCT). 3 deaths have unknown causes. The overall actuarial survival is 40 years of age: 75.1% +/-4.85. [This means if you have DBA, your statistical chances of reaching age 40, regardless of treatment, is about 75%. Note that this is according to the data in the DBAR, so the figures are only as good as the data. In other words, get your info in the Registry!!!] For steroid-maintainable patients, it's 86.7% +/- 7.0%. For transfusion-dependent patients, it's 57.2% +/- 8.9%. This figure show so low because 7 of the people in these numbers were transfusion dependent patients who died from complications of SCT. Gene Discovery: RPS19 mutations in 20-25% of inherited and sporadic cases. There are other DBA genes - ?chromosone 8p and new genes still unmapped. DBA is clinically and genetically heterogenous. The pathophysiology of DBA is unclear. [Here Dr. V showed several pedigrees (which are like family trees but they show genetic traits) of families that had an ancestor which had DBA tendencies but no anemia, and then descendents with various degrees of DBA.] % of cases locus gene cloned gene product DBA1 -25% 19q13.2 yes RPS19 DBA2 -2% TBD yes TBD DBA3 rest unknown no unknown |
| Outcomes of Stem Cell Transplant, Remission, Etc. |
 |  |  |