Stem Cell Transplantation

The physicians at the University of Chicago caring for stem cell transplants are writing in response to the national coverage decision for stem cell transplantation (110.8.1).

We believe that coverage for an autologous or allogeneic stem cell transplant should be comprehensive and reflect the entire set of services necessary for the procedure. The intensity of the procedure entails multiple steps for pre and post-transplant care including:

1. Evaluation of patient and/or donor
a. Pretransplant assessment such as pulmonary, cardiac, and infectious evaluation
b. Allogeneic transplant specifically require HLA typing of the patient, donor, and searching a volunteer registry when no HLA match is available
2. Procuring donor stem cells with chemotherapy, colony-stimulating factors and/or bone marrow harvest. For unrelated and cord blood stem cells sources, additional costs for procurement accrue
3. Measurement and cryopreservation (when needed) of stem cell product
4. Preparative chemotherapy
5. Stem cell infusion
6. Post-transplant care

1. This may require hospitalization and frequent follow-up visits. Most centers have frequent patient visits until 100 days after the transplant.
2. Disease reevaluation
3. Necessary post-transplant supportive care, such as growth factors, infectious monitoring and treatment (e.g. CMV monitoring and treatment)

In addition, we would like to specifically comment on the coverage guidelines on transplant indications for allogeneic transplant. The guidelines indicate only that treatment for “leukemia, leukemia in remission, aplastic anemia and SCID” are covered and multiple myeloma is not covered. We believe the present guidelines do not reflect the present literature or optimal care. For example, additional conditions for which allogeneic transplant represents a reasonable indication include:

1. Myelodysplasia
2. Myelofibrosis (Chronic Idiopathic and other Myelofibrotic conditions) or other myeloproliferative disorders.
3. Relapsed or refractory non-Hodgkins Lymphoma
4. Relapsed or refractory Hodgkins Lymphoma
5. Chemotherapy/medication induced irreversible aplasia
6. High risk multiple myeloma

Sincerely,

The University of Chicago
Section of Hematology and Transplantation

Andrew Artz, MD, MS
Christopher Daugherty, MD
Lucy Godley, MD, Ph.D
Richard Larson, MD
Olotayosi Odenike, MD
Michael Thirman, MD
Elizabeth Rich, MD, Ph.D
Sonali Smith, MD
Wendy Stock, MD
Koen van Besien, MD
Todd Zimmerman, MD

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THE FOLLOWING IS SUBMITTED ON BEHALF OF THE AMERICAN SOCIETY OF HEMATOLOGY AND THE AMERICAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION
_____________________________________________
FROM: Nelson Chao, MD, President
American Society for Blood and Marrow
Transplantation

James M. George, MD, President
American Society of Hematology

SUBJECT: Re-Definition of Stem Cell Transplantation

We appreciate the opportunity to comment on this National Coverage Determination (NCD) regarding a re-definition of stem cell transplantation. The rapid evolution of the field of hematopoietic stem cell transplant makes this an appropriate juncture to re-examine the definition of stem cell transplantation.

General Comments:

1. Consideration should be given to separating allogeneic from autologous stem cell transplant. Section 110.8.1 correctly states that “Autologous stem cell transplants (AuSCT) must be used to effect hematopoietic reconstitution following severely myelotoxic doses of chemotherapy (HDCT) and/or radiotherapy used to treat various malignancies.” This can also be true for allogeneic transplant. More often, however, allogeneic transplant is used to either provide additional therapy to the underlying malignancy via the effect of the donor immune system or to correct an underlying immune or inherited problem via the normal function of the donor hematopoietic stem cells. Another consideration in separating allogeneic from autologous stem cell transplant is that the type, acuity and duration of care differ significantly for the two therapies.

2. The major components of hematopoietic stem cell transplant are donor identification and evaluation, patient evaluation, stem cell acquisition, delivery of the preparative regimen, stem cell infusion, management until engraftment and post-transplant care.

3. It would be desirable to separate hematopoietic stem cell acquisition from the transplant itself. For autologous stem cell acquisition this should encompass either bone marrow harvest or peripheral blood stem cell collections. Chemotherapy is often delivered to the patient prior to autologous peripheral blood stem cell harvest. Since such chemotherapy is given with the purpose of cytoreduction of the malignancy as much as to enhance mobilization of stem cells, it should be excluded from stem cell acquisition. It would be reasonable to include growth factor administration such as filgrastim as part of collection of either allogeneic or autologous stem cell collection. Allogeneic stem cell acquisition should include bone marrow, peripheral blood stem cell and umbilical cord blood as all are standard sources of hematopoietic stem cells.

4. The start of the transplant should be considered the first day of delivery of the preparative regimen. While the preparative regimen has traditionally been performed as an inpatient, it should be recognized that preparative regimen, the transplant and much if not all of the post-transplant care may be safely delivered as an outpatient in the appropriate setting.

5. We agree that the preparative regimen and the stem cell transplant are both integral to the therapy. The intent of the preparative regimen may vary by the type of transplant. With autologous stem cell transplant, severely myelotoxic doses of chemotherapy and radiotherapy will be used. This may not be universally true for allogeneic transplant as the intent in some situations is to achieve engraftment to either allow an immunologic effect of the donor graft against malignancy or to correct an immune or genetic deficiency.

6. The end of the transplant is more difficult to define, but can generally be considered engraftment. We suggest that attainment of 500 neutrophils per microliter of blood may be a reasonable working definition. Recognition that post-transplant care does not stop at engraftment is important, and anything post- engraftment should be considered post-transplant care.

7. Finally, we feel that the covered indications for stem cell transplant are overly restrictive and do not reflect standard of care. Additional indications for allogeneic stem cell transplant should include myelodysplatic syndrome, non-Hodgkin’s lymphoma and multiple myeloma. Germ cell tumors should be considered as an additional indication for autologous transplant.

Thank you for the invitation to submit these comments. We will be happy to answer any questions or respond, as needed, with additional information.

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I appreciate your opening the issue of transplant definition for comments. I support a comprehensive definition for autologous and allogeneic transplants. For autologous transplants, this would mean coverage from mobilization chemotherapy through transplantation to complete hematologic engraftment. For allogeneic transplants, this would mean coverage for identification of a suitable donor through transplantation and immunosuppression to discontinuation of all immunosuppression and supportive antibiotics. Furthermore, I urge you to open a discussion of what indications are covered under CMS. As I understand coverage right now, allogeneic transplantation is covered for a diagnosis of acute myeloid leukemia, but not for multiple myeloma. Patients with myelodysplastic syndromes, therefore, fall into a grey zone of not being on the covered list, but not being on the "not covered" list either. This leads to a case-by-case analysis at the local level, or to automatic refusal of services. Allogeneic transplantation is a potentially curative treatment for patients with myelodysplastic syndromes. A systematic assessment of coverage for all autologous and allogeneic transplants is urgently needed.Thank you for your consideration.

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high dose chemotherapy with hematopoietic stem cell transplant. (HDC-HSCT)

I suggest that you consider the process beginning at stem cell mobilization and continuing through marrow engraftment. Currently, the traditional definition of just the conditioning regimen (HDCTX +/- Radiation) and stem cell reinfusion is the normative definition.

If you move to a more comprehensive definition, you should also include the outpatient portions of treatment and consider providing a financial incentive to perform as much of the treatment in the outpatient setting as possible. Currently, CMS incentivizes for inpatient transplant and penalizes programs that can perform transplants in the outpatient setting.

Finally, while you're looking at transplant, consider extending coverage to tandem transplant in myeloma when a compete response is not achieved after the first transplant. Efficacy was scientifically proven by the French Myeloma group in Dec. 25, 2003 NEJM

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