Revisiting the History of Haploidentical Transplantation

The year 2019 marks 50 years since Dr. William Dameshek, a pioneer in the field of hematology, passed away. As the founding editor of Blood, his accomplishments and contributions to hematology are extensive. Among other things, he is well-known for developing a unifying concept of myeloproliferative disorders.¹  He was an early user of nitrogen mustard for hematologic malignancies²  and one of the first to incorporate its use in autologous transplantation.³ 

Dr. Dameshek’s visionary approach to hematology, particularly in the field of transplantation, cannot be overstated. He established his career in Boston, arriving at The Mount Sinai Hospital in New York in 1966. He was directing his efforts toward the achievement of clinical bone marrow transplantation (BMT) in aplastic anemia (AA) and leukemia patients when he passed away from a stroke on October 6, 1969. Several years later, the Center for International Blood and Marrow Transplant Research (CIBMTR) contacted our program to follow up on a patient who received a stem cell transplant in 1969 under the care of Dr. Robert Taub. At the time Dr. Taub was an attending physician working closely with Dr. Dameshek. In an interview, Dr. Taub indicated that after Dr. Dameshek did his initial work on transplantation in Boston he wanted to further expand on its utility at Mount Sinai; Dr. Taub, with another young associate, Dr. Arnold Rubin, continued the efforts under Dr. Dameshek’s tutelage.

Unable to find medical records going that far back, Mount Sinai’s BMT program performed an internet search of the patient’s name and found an obituary dated 1999. The funeral was associated with a place of worship in Connecticut that provided the family’s information, and the patient’s daughter and son-in-law were interviewed. The son-in-law was friends with Phyllis Hurtwitz, a hematology fellow at Mount Sinai who had convinced the patient to visit Dr. Dameshek. The son-in-law recalled the encounter with Dr. Dameshek vividly, describing him as a physically impressive man.

The patient’s daughter indicated that her brother was thought to be a “better” match for her mother. She also mentioned that the transplantation was initially not successful and that the doctors had to use her cells as well, but neither Dr. Taub nor Dr. Rubin endorsed this information. Dr. Rubin recalled that the chromosome testing on the patient’s blood sample after transplantation showed a female complement. The Human Genetics Program at our institution has no cytogenetic records going that far back. The patient died in 1999, at the age of 90. Her only medical problems were osteoporosis, a hip replacement, and a shoulder injury from a robbery that never quite healed. Her son-in-law recalled that the patient had “low platelets” and had occasional gum bleeding. The institution where she received her end-of-life care did not have any laboratory values dating back to 1999.

In 1968, Dr. George Mathé and colleagues reported the first clinical use of pretransplant antithymocyte globulin (ATG) in a 42-year-old man with acute myeloid leukemia who received a bone marrow graft from his brother. One month post-transplantation, there was complete restoration of hematopoiesis.⁴  The report by Dr. Taub and senior author Dr. Dameshek appears to be the first use of ATG in a nonleukemic AA patient and may also represent the first documentation of haploidentical transplantation in AA.⁵