Hematopoietic stem-cell transplantation (HSCT) refers to a procedure in which hematopoietic stem cells are infused to restore bone marrow function in cancer patients who receive bone-marrow-toxic doses of cytotoxic drugs, with or without whole-body radiation therapy. Hematopoietic stem cells may be obtained from the transplant recipient (autologous HSCT) or from a donor (allogeneic HSCT). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood shortly after delivery of neonates. Although cord blood is an allogeneic source, the stem cells in it are antigenically “naïve” and thus are associated with a lower incidence of rejection or graft-versus-host disease (GVHD).

For the purposes of this policy, the term “reduced-intensity conditioning” will refer to all conditioning regimens intended to be non-myeloablative, as opposed to fully myeloablative (traditional) regimens.

For individuals with non-Hodgkin lymphoma (NHL) B-cell subtypes considered aggressive (except mantle cell lymphoma), either allogeneic HSCT using a myeloablative conditioning regimen or autologous HSCT may be considered medically necessary for either of the following:

• As salvage therapy for individuals who do not achieve a complete remission (CR) after first-line treatment (induction) with a full course of standard-dose chemotherapy; or
• To achieve or consolidate a CR for those in a chemo-sensitive first or subsequent relapse. 

For patients with mantle cell lymphoma:

• Autologous HSCT may be considered medically necessary to consolidate a first remission.
• Allogeneic HSCT, myeloablative or reduced-intensity conditioning, may be considered medically necessary as salvage therapy.
• Autologous HSCT is considered experimental/investigational and therefore, non-covered, as salvage therapy. Scientific evidence does not support this treatment.
• Allogeneic HSCT is considered experimental/investigational and therefore, non-covered, to consolidate a first remission. Scientific evidence does not support this treatment.

For patients with NHL B-cell subtypes considered indolent, either allogeneic HSCT using a myeloablative conditioning regimen or autologous HSCT may be considered medically necessary for the following:

• As salvage therapy for individuals who do not achieve CR after first-line treatment (induction) with a full course of standard-dose chemotherapy; or
• To achieve or consolidate CR for those in a first or subsequent chemosensitive relapse, whether or not their lymphoma has undergone transformation to a higher grade.

Reduced-intensity conditioning (RIC) allogeneic HSCT may be considered medically necessary as a treatment of NHL in individuals who meet criteria above for an allogeneic HSCT but who do not qualify for a myeloablative allogeneic HSCT.

Either autologous HSCT or allogeneic HSCT is considered experimental/investigational and therefore, non-covered, as scientific evidence does not support these treatments:

• As initial therapy (i.e., without a full course of standard-dose induction chemotherapy) for any NHL;
• To consolidate a first CR for individuals with diffuse large B-cell lymphoma and an International Prognostic Index score that predicts a low- or low-intermediate risk of relapse;
• To consolidate a first CR for those with indolent NHL B-cell subtypes.

Tandem transplants are considered experimental/investigational, and therefore, non-covered, to treat individuals with any stage, grade, or subtype of NHL.

For individuals with peripheral T-cell lymphoma:

• Autologous HSCT may be considered medically necessary to consolidate a first complete remission in *high-risk peripheral T-cell lymphoma.
• Autologous or allogeneic HSCT (myeloablative or reduced-intensity conditioning) may be considered medically necessary as salvage therapy.
• Allogeneic HSCT is considered experimental/investigational, and therefore, non-covered, to consolidate a first remission. Scientific evidence does not support this treatment.

*High-risk peripheral T-cell lymphoma is defined as one of the histologic subtypes as follows:

• Nodal: peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), anaplastic lymphoma kinase negative anaplastic large cell lymphoma (ALK- ALCL) or angioimmunoblastic lymphoma (AIL). High-risk patients may also include the rare patient with ALK+ALCL who is refractory to conventional chemotherapy.
• Extranodal: T/NK cell lymphoma nasal type, enteropathy-type T-cell lymphoma, hepatosplenic T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma.

RIC would be considered an option in individuals who meet criteria for an allogeneic stem-cell transplant (SCT) but whose age (typically older than 55 years) or comorbidities (e.g., liver or kidney dysfunction, generalized debilitation, or prior intensive chemotherapy) preclude use of a standard conditioning regimen.

In individuals who qualify for a myeloablative allogeneic hematopoietic HSCT on the basis of overall health and disease status, allogeneic HSCT using either myeloablative or RIC may be considered. However, a myeloablative conditioning regimen with allogeneic HSCT may benefit younger individuals with good performance status and minimal comorbidities more than allogeneic HSCT with RIC.

Available scientific evidence does not permit conclusions concerning the effect of hematopoietic stem-cell transplantation for non-Hodgkin lymphomas for services considered experimental/investigational in this policy.