JAMA: Use of a lower intensity bone marrow transplantation method showed
promising results among 30 patients (16-65 years of age) with severe
sickle cell disease, according to a study in the July 2 issue of JAMA.
Myeloablative (use of high-dose chemotherapy or radiation) allogeneic
hematopoietic stem cell transplantation (HSCT; receipt of hematopoietic
stem cells “bone marrow” from another individual) is curative for
children with severe sickle cell disease, but associated toxicity has
made the procedure prohibitive for adults. The development of
nonmyeloablative conditioning regimens (use of lower doses of
chemotherapy or radiation to prepare the bone marrow to receive new
cells) may facilitate safer application of allogeneic HSCT to eligible
adults, according to background information in the article.
Matthew M. Hsieh, M.D., of the National Institute of Diabetes and
Digestive and Kidney Diseases, Bethesda, Md., and colleagues explored a
nonmyeloablative approach in a pilot group of 10 adults with severe
sickle cell disease, using a simplified HSCT regimen (with stem cell
donation from a immunologically matched sibling), that had few toxic
effects, yet all patients continued taking immunosuppression medication.
The researchers have since revised the protocol to include an option to
stop immunosuppression after 1 year in selected patients (those with
donor CD3 engraftment of greater than 50 percent and normalization of
hemoglobin). In this report, the authors describe the outcomes for 20
additional patients with severe sickle cell disease, along with updated
results from the first 10 patients. All 30 patients (ages 16-65 years)
were enrolled in the study from July 2004 to October 2013.
As of October 25, 2013, 29 patients were alive with a median
follow-up of 3.4 years, and 26 patients (87 percent) had long-term
stable donor engraftment without acute or chronic graft-vs-host disease.
Hemoglobin levels improved after HSCT; at 1 year, 25 patients (83
percent) had full donor-type hemoglobin. Fifteen engrafted patients
discontinued immunosuppression medication and had no graft-vs-host
disease.
The average annual hospitalization rate was 3.2 the year before HSCT,
0.63 the first year after, 0.19 the second year after, and 0.11 the
third year after transplant. Eleven patients were taking narcotics
long-term at the time of transplant. During the week they were
hospitalized and received their HSCT, the average narcotics use per week
was 639 mg of intravenous morphine-equivalent dose. The dosage
decreased to 140 mg 6 months after the transplant.
There were 38 serious adverse events including pain, infections,
abdominal events, and toxic effects from the medication sirolimus.
“In this article, we extend our previous results and show that this
HSCT procedure can be applied to older adults, even those with severe
comorbid conditions …” the authors write. “These data reinforce the low
toxicity of this regimen, especially among patients with significant
end-organ dysfunction.”
“In this series of patients who underwent a simplified HSCT regimen
to date, … reversal of sickle cell disease phenotype was achieved in the
majority of patients. Engrafted patients continued to be disease-free
and without graft-vs-host disease,” the researchers write. “Further
accrual and follow-up is required to assess longer-term clinical
outcomes, adverse events, and transplant tolerance.”
(doi:10.1001/jama.2014.7192; Available pre-embargo to the media at http://media.jamanetwork.com)
Editor’s Note:
This work is supported by the intramural research program of the
National Institute of Diabetes and Digestive and Kidney Diseases and the
National Heart, Lung, and Blood Institute at the National Institutes of
Health. All authors have completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest and none were reported.
There will also be a digital news release available for this study, including the JAMA
Report video, embedded and downloadable video, audio files, text,
documents, and related links. This content will be available at 3 p.m.
CT Tuesday, July 1 at this link.
Editorial: Reconsideration of Age as a Contraindication for Curative Therapy of Sickle Cell Disease
Allison A. King, M.D., M.P.H., and John F. DiPersio, M.D.,
Ph.D., of the Washington University School of Medicine, St. Louis,
comment on the findings of this study in an accompanying editorial.
“In a population of relatively older adults with sickle cell disease,
these findings offer hope. Based on these exciting results, the role of
age as a contraindication for offering adults with sickle cell disease
and a matched sibling the chance of curative allogeneic stem cell
transplant should be reconsidered.”
(doi:10.1001/jama.2014.7193; Available pre-embargo to the media at http://media.jamanetwork.com)
Editor’s Note:
The authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest and none were reported.