Question

Matt was a healthy child, until the summer of his seventh year, when his father noticed that he was unusually pale. Closer examination revealed small petechiaeon his son’s arms and legs.He took Matt to his pediatrician. She performed a physical examination, which did little more than confirm that Matt was indeed very pale, and had skin petechiae.Blood tests were ordered, with results that indicated that Matt was very anemic. His hemoglobin was 7.4 g dl-1(normal = 10-15 g dl-1)and his platelet count was 25,000 μl-1(normal = 150,000-300,000 μl-1). His white blood cell count was also lower than normal. Matt was referred to a hematologist for a bone marrow biopsy.The bone marrow biopsy found very few cells present, with platelet, red cell and white cell precursors virtually absent.A diagnosis of aplastic anemia of unknown cause was made. Untreated aplastic anemia is universally fatal, but can be cured by a bone marrow transplant,provided a suitable donor is identified. Fortunately, Matt’s and his 11-year-old brother Andrew had identical HLA haplotypes. Matt was admitted to the Comprehensive Care Center for Cancer and Blood Disorders at Dayton Children's Hospital.   He was given a treatment course of intravenous horse anti-thymocyte globulin (ATG), fludarabine, and cyclophosphamide.Following this treatment course, he then received by central venous catheter bone marrow cells (2 x 108cells per kg body weight)that had been obtained from his brother’s iliac crests. Following the transplant,he was started on a course of cyclosporine A (CsA).Matt did well for the first four weeks following engraftment; however, on the 29th day he developed a patchy bright red rash, first on his neck and face, then also on his palms and soles.This was accompanied by the development of a watery diarrhea. He did not develop a fever, nor did he show signs of jaundice. He had a normal heartbeat and his lungs were clear. His liver and spleen were not enlarged, and liver function tests (ALP & AST) were normal.Matt was treated with corticosteroids and his skin rash faded over the next several days. Meanwhile, his diarrhea became more profuse, with evidence of intestinal bleeding. He was then given intravenous rabbit ATG for three consecutive days. This brought his diarrhea under control, and resolved the intestinal bleeding. He showed steady improvement from this point, and was released from the hospital nine weeks to the day after his bone marrow engraftment. He remains under continuing treatment with low doses of corticosteroid, and visits an outpatient clinic weekly to monitor his status.

Questions:

1.) Prior to his bone marrow engraftment, Matt was treated with intravenous horse anti-thymocyte globulin (ATG), fludarabine, and cyclophosphamide.

a.) What is does this treatment do and...

b.) Why is this treatment necessary (what happens if it is not done?).

2.) The rash and diarrhea that Matt developed were symptoms of a complication with his bone marrow engraftment. What is this complication, and how does it cause these symptoms?

3.)In this case, there was no processing of the donated bone marrow before it was administered to Matt. What kinds of treatments can be done to the bone marrow before it is transplanted to lessen the likelihood of the complication Matt suffered from occurring?

4.) BecauseMatt and his brother Andrew had the same HLA haplotypes, the complications that arose for Matt were not as severe as they would have been had a less well-matched donor (like perhaps his father) been used. But, why did they occur at all?

5.)   What is the long-term prognosis for Matt, and what challenges might he face? Be detailed in your answer.

Answer 1

1) Aplastic anemia occurs when there is a damage to bone marrow ,results in decreased production of red blood cells. Bone marrow is a spongy tissue present inside the bone and is responsible to produce stem cells, other blood cells like red blood cells, white blood cells and platelets are produced by the stem cells.Aplastic anemia is commonly occurs in certain conditions like:

- viral infections Epstein barr virus, cytomegalovirus, HIV that suppresses bone marrow.

- Autoimmune diseases that affects bone marrow.

- Cancer drugs given in chemotherapy and radiation therapy damaged the healthy bone marrow cells.

- Prolonged exposure to certain toxic chemicals like benzene,pesticides results in aplastic anemia.

a) Anti lymphocytic immunoglobulin is prepared by inoculating horse with human thymocytes antigen to induce horse immune system to produce immunoglobulins to human thymocytes. It is used as a immunosuppression drug. It is administered to patient to suppress his immune system to prevent bone marrow rejection and as a treatment modality for aplastic anemia.

b) If immunosuppression not given prior to the surgery the chances of graft versus host disease and end up with graft rejection.

2) Diarrhea and rashes after a bone marrow transplantation accompanying with jaundice indicates complication of allogenic hematopoietic cell transplantation. It indicates a serious life threatening immune reactions towards the graft. Engraftment syndrome is a complication that can occur after a bone marrow transplant.

3) Inorder to reduce graft versus host reactions HLA haplotype assessment is done.The gold standard of selecting donor is based on the related donors like parents,siblings. In this case allogenic graft failure happens secondary to underlying viral infections. This infection may be a underlying reason for diarrhea and intestinal bleeding.