HemOnc Today's PharmAnalysis
HemOnc Today's PharmAnalysis
July 10, 2018
5 min read

Novel transplant protocol potentially curative approach for sickle cell disease

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Damiano Rondelli

A small cohort of patients with sickle cell disease underwent successful hematopoietic stem cell transplantation from non-HLA matched donors, a group previously thought to be incompatible.

Damiano Rondelli, MD, Michael Reese professor of hematology, chief of hematology and oncology, and director of the blood and marrow transplant program at The University of Illinois at Chicago, performed haploidentical HSCT for 10 adults with sickle cell disease.

Participants received peripheral blood stem cells. Two initial patients underwent conditioning with alemtuzumab (Lemtrada; Sanofi Genzyme) and total body irradiation 3Gy, along with cyclophosphamide in the posttransplant setting. These patients failed to engraft.

The remainder of the cohort underwent conditioning as per a modified version of a protocol developed at Johns Hopkins University, using donor peripheral blood stem cells, a low-intensity chemotherapy, total body irradiation 3Gy and posttransplant cyclophosphamide. One patient in this group lost the graft. Two developed GVHD; one case was severe, and the other was mild and transient.

At median follow-up of 16 months (range, 11-29), seven patients remained alive and fully engrafted with donor cells.

HemOnc Today spoke with Rondelli about the findings, the next steps in this research and how this approach may benefit patients with sickle cell disease.


Question: How does this approach differ from traditional sickle cell disease treatment?

Answer: Traditional treatment of sickle cell disease is mostly supportive therapy with transfusions and hydroxyurea, with the goal to reduce pain and delay organ damage. Traditional treatment is helpful but not really curative. This is a curative approach. Bone marrow transplant has been performed for many years for patients with sickle cell disease, especially children, but it is not the standard of care because of the many risks — particularly among adults — due to toxicity caused by chemotherapy. The new component in our study is that patients with sickle cell disease can be transplanted from only half-compatible donors with a reduced-intensity preparation of chemotherapy and radiation. This strategy limits the risk for morbidity and mortality for patients and still achieves a very good result. More than 80% of our patients are cured of sickle cell disease with this approach. This is our second study. The first was done with matched related donors, meaning a compatible brother or sister of the patient donated the stem cells. In that setting, we used no chemotherapy in the transplant and achieved very high rate of cure without major toxicity. The study we just published was is in the haploidentical setting. Donors don’t need to be fully matched. They can be only half compatible. The reason this is relevant is that most patients with sickle cell disease are African-American and it is rare to find a matched donor for these patients unless they have a brother or sister who is a full match. The probability is less than 20%. By utilizing only half-matched related donors, we can expand the donor pool to almost any family member and potentially offer a transplant to more than 90% of patients.


Q: Why hasn’t this been done before?

A: Haploidentical transplant has only been developed in the last few years. We now do it routinely in blood cancers, such as leukemia, myelodysplastic syndrome and others. However, there are limited data for its use in sickle cell. There are only two studies where it has been done for adults. The numbers are still small because people are reluctant to expose patients to possible risk. We expect haplo-transplant to grow quickly in the sickle cell community.


Q: Your data set thus far is small. Do you intend to evaluate this in a larger cohort, and what kind of results do you expect to see?

A: The first few patients who received the haploidentical transplant received it with reduced intensity. These data were published in 2012 by Johns Hopkins, where this kind of incompatible transplant was invented. They showed that fewer than 60% of patients had a full engraftment. This was a good percentage, but obviously not close to 100%. The good news is that this transplant was safe and not toxic. The only other study was done by NIH. They used a slightly different approach. It was also nontoxic, and they showed about 60% success. This was acceptable, but we tried to improve upon it using a modified version of the Hopkins protocol. We made a couple changes to make it more effective. We had 83% engraftment with very little toxicity. I expect now that other groups doing clinical trials using low-intensity chemotherapy will publish their data soon. My expectation is that this type of transplant will have about an 80% success rate without major complications in adults with sickle cell disease.


Q: Do you have any thoughts about how or when to standardize the approach, and who will do that?

A: At the last American Society of Blood & Marrow Transplant meeting, doctors from Johns Hopkins presented their data with a protocol similar to what we used, but with a slightly higher dose of chemotherapy. These modifications or variations of the same protocol make people feel more comfortable because they can improve on previous results. At the end of the day, most of these protocols are similar, with reduced intensity and low toxicity. Standardizing will require a comparative study, which I don’t know will be done anytime soon because of small volume of patients.



Q: What is the impact of this approach on patients’ quality of life?

A: The quality of life of these patients is significantly improved. They often end up off any treatment for sickle cell disease, and they achieve a much better performance status, which I think is relevant for these patients.


Q: How about the potential drawbacks or obstacles?

A: We did present a real-life picture at this time of what the transplant is. An interesting finding is that 30% of patients are not covered for this transplant by insurance. With more data coming out and results being shared, it will improve coverage. In addition to that, the major finding is that 30% of patients who found a donor refused or preferred to delay the transplant. Patients are still afraid and uncertain about this procedure. They waited and delayed. We need to improve the awareness of what this is and what the results are. A lot of patients in the sickle cell community have been suffering their whole lives, with major organ dysfunction. They are afraid that the chemotherapy used in the transplant might cause a risk of dying they don’t want to take. That means that, for our part, we need to be better messengers or ambassadors of our results.


Q: If patients are not aware of this procedure, do you also need to do a better job of informing clinicians so they can spread the word?

A: Yes. Any doctor who takes care of patients with sickle cell disease knows how difficult it is to make these patients feel better. In the community, many of the doctors who see these patients are not hematologists who specialize in sickle cell or transplantation. Some are internists. They deal with pain crisis, renal dysfunction, hemolytic anemia, strokes and other organ dysfunction. They aren’t aware of transplant as a possible cure. Having these doctors, not only the hematologists but the internal medicine doctors, aware would be a major advantage for this patient population. – by Rob Volansky



Saraf SL, et al. Biol Blood Marrow Transplant. 2018;doi:10.1016/j.bbmt.2018.03.031.

For more information:

Damiano Rondelli, MD, can be reached at The University of Illinois at Chicago, 840 S. Wood St. (820-E-CSB), Chicago, IL 60612; email: drond@uic.edu.

Disclosure: Rondelli reports no relevant financial disclosures.