(All the articles published in past are available at www.shyamhemoncclinic.com)
Question: Dr. Chiragbhai, thank you for explaining in last part about causes and diagnosis of aplastic anemia. What is the current best treatment for this serious disorder?
Ans: Before the advent of current therapies, most patients died in one year, generally in first few months. Steroids do not work in aplastic anemia, in fact lead to more infections. Some doctors in India still start these patients on steroids, considering autoimmune disease. This practice is to be strongly discouraged. Current treatment decisions are based on following factors:
2. Availability of HLA matched sibling donor
3. Comorbidities, Fitness
Que: How do you use these factors in decision making?
Ans: Most important are first two factors.
1. Age < 20 : Stem cell transplant is preferred, if there is a matched brother or sister.
2. Age 20-50 : stem cell transplant is preferred if there is a matched brother or sister, and patient is very fit with no major comorbidity.
3. Patients above age 50 or not meeting above criteria, should be treated with ATG and cyclosporine. ATG can be given up to age 80 if patient is otherwise well.
Transplant is preferred when feasible, for following important reasons:
1. Transplant leads to most rapid and reliable recovery of blood counts, within 14 days in most cases, especially neutrophils. ATG may take 3-6 months for recovery.
2. Response rate of transplant is much higher than with ATG, 90% Vs 50%.
3. ATG treatment is associated with long term risk of serious bone marrow disorders, such as MDS, AML, PNH, in about 20% patients. This risk is not seen with transplant.
Drawback of transplant is initial risk especially gvhd, need for very active monitoring and treatment in first few months, and cost. All these risks are much lower in younger patients.
Que: Ok. So transplant is a very rapid way of raising counts, but needs longer commitment to treatment, good health, and HLA matched sibling, and is more expensive. ATG and cyclosporine on the other hand are comparatively easy treatment with minimal post treatment monitoring and less cost, but provides a much slower raise in counts, and has long term negative effects.
Ans: Yes that is a good comparison. Also, it is important to note that since transplant allows much faster recovery, it is the preferred treatment in patients who present with significant infections like fungal infection.
Cost of transplant is about 10-12 lac, whereas cost of ATG and cyclosporine course is about 5-9 lac (lower cost is with Indian brand of ATG). However in an individual patient, decision is not easy, especially if age over 20-30. Patient should be given both options. If absolute neutrophil count is below 200 (very severe aplastic anemia category), transplant is certainly preferred as it allows faster improvement in counts. This is important as patients with such severe neutropenia frequently die from sepsis in first one to two months.
For patients who do not respond to ATG or relapse, transplant is the preferred option. Second option in such cases is repeat course of ATG or alemtuzumab. One other very recent option is tablet eltrombopag. This drug is approved for ITP but has shown some good initial results in refractory aplastic anemia.
A recent trial showed that horse ATG is better than rabbit ATG in first line treatment.
Supportive care in form of blood transfusions (with leukocyte filter), G-CSF, prophylactic antibiotics should be given. Blood transfusions should be minimized to reduce risk of alloimmunization and graft rejection. Success of transplant correlates with time from diagnosis, likely related to number of transfusions. Hence, it is better to transplant as early as possible, rather than delay for several months.
Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 079 26754001. Diplomate American Board of Oncology and Hematology. Ahmedabad. firstname.lastname@example.org Shyam Hem-Onc Clinic. 402 Galaxy, Near Shivranjani, Opp Jhansi ki Rani BRTS, Ahmedabad. www.shyamhemoncclinic.com