Allogeneic Bone Marrow Transplant for Lymphomas: Hodgkin Lymphoma and Non-Hodgkin Lymphoma

Allogeneic bone marrow transplantation is an important and potentially curative modality in treatment for a number of hematologic malignancies, especially so in cases of lymphomas, for instance Hodgkin Lymphoma and Non-Hodgkin Lymphoma. These lymphomas affect the lymphocytes—a type of white blood cell responsible for adequate defense of the body. Allogeneic transplant is a procedure which replaces the diseased or cancerous bone marrow with healthy hematopoietic stem cells from a compatible donor. It enables long-term remission, or in some cases, cures with a patient who has failed other treatments. 

Understanding Lymphomas

Lymphomas develop in the lymphatic system, forming an important part in the working of the immune system, including the lymph nodes, spleen, and bone marrow. There are two main types:

1. HL (Hodgkin Lymphoma): This lymphoma is characterized by the presence of specific Reed-Sternberg cells in the lymph nodes. Hodgkin lymphoma is often linked with symptoms such as fever, night sweats, weight loss, and swollen lymph nodes. Initial treatment mostly is performed with the use of chemotherapy and radiation therapy. For those patients, however, in which the incidence of the disease shows a relapse or a poor response to the treatments mentioned above, an allogenic bone marrow transplant may be the best option.
2. Non-Hodgkin Lymphoma: Non-Hodgkin lymphoma is a heterogeneous group of lymphoid malignancies, including very indolent and highly aggressive types. Treatments are mostly chemotherapy, immunotherapy, and targeted therapies. For patients with aggressive subtypes of NHL whose diseases are drug-resistant, an allogenic transplant gives them an opportunity to replace their drug-damaged bone marrow with normal donor stem cells, giving long-term survival with potential cure of the cancer.

The indications for allogeneic BMT in patients are:

• Relapsed or Refractory Lymphoma: For patients whose lymphomas have recurred after prior treatments or are unresponsive to standard therapies, an allogeneic BMT provides them with the opportunity for a cure following replacement of the patient's neoplastic bone marrow with a healthy, cancer-free hematopoietic stem cell. A new and healthy immune system is then reconstituted with the capacity to fend off lingering cancer cells.
• High-Risk Lymphoma: Advanced stage diseases or specific genetic mutations can be treated best by an Allogenic transplant. Such treatment definitely has the potential for long-term remission and could improve the overall survival rate with the infusion of healthy hematopoietic stem cells from a donor.

The Allogeneic BMT Procedure

Several critical steps are involved in this procedure:

• Pre-transplant conditioning: The patient undergoes an intensive conditioning regimen with high-dose chemotherapy and/or total body irradiation before transplantation. The goals of conditioning are the destruction of malignant cells in the marrow, the abolition of the host's immune system in order to prevent allorejection, and making space available for engrafting the newly introduced hematopoietic stem cells.
• Donor Matching and Selection: Basically, an allogenic BMT needs a compatible donor to be searched for. The best donor is usually a sibling, but unrelated donors may also be found through the National Marrow Donor Program or even umbilical cord blood units. Proper matching of HLA is vital to minimize the risk of GVHD when the donor's immune cells attack the tissues of the recipient.

Stem Cell Infusion The patient now receives an infusion of the healthy donor's hematopoietic stem cells directly into their bloodstream. The cells will migrate to the bone marrow and start an engraftment process that will begin the production of new red blood cells, white blood cells, and platelets.

On the other hand, post-transplant care and monitoring are needed to identify early the development of possible complications like infection or GVHD in a patient. The supportive care includes prophylactic antibiotics, antifungal treatments, and the ongoing immunosuppressive therapy balancing between controlling GVHD and maintaining graft versus tumor effect.

Challenges and Complications of Allogeneic BMT

Notwithstanding its potential benefits, Allogeneic BMT has some risks:

• Graft-versus-Host Disease (GVHD): This is one of the worst complications, where the newly transplanted immune cells recognize the recipient's body as foreign and start attacking it. GVHD can be acute or chronic and can involve the skin, liver, gut, or many other organs. Treatment of GVHD may require long-term immunosuppression.
• Infections: A patient who undergoes allogeneic BMT is substantially immunocompromised and readily victimized by infection. Hence, prophylactic antibiotics and antifungal are very important during the recovery phase to prevent fatal infections that may be life-threatening.
• Graft Failure: In some cases, after the transfusion of hematopoietic stem cells, there may be failure to engraft properly; the clinical aspect is that of graft failure. This may require a second transplant or some other type of intensive treatment in order to ensure healthy blood cell production.
• Long-Term Effects: Survivors from allogeneic BMT are bound to suffer from secondary cancers, organ damage, and infertility. Continuous follow-up is very important for the management of these potential problems. Advances in Allogeneic BMT for Lymphomas

Recent advances in allogeneic BMT have improved the outcome of patients with lymphoma:

RIC, meaning reduced-intensity conditioning, is one that involves lower dosage of chemotherapy and radiation; hence, the procedure will be less toxic, more so in the elderly or when associated with co-morbidities. RIC has made allogeneic BMT an option for a greater number of patients.

• Novel GVHD Management: More novel techniques in the management of GVHD include highly selective immunosuppressive therapies and cellular therapy –based strategies, which retain the favorable graft-versus-tumor effect but are less damaging owing to GVHD. Such novel techniques:  Gene Therapy: Gene therapy techniques are being investigated to compliment Allogenic BMT by correcting genetic defects that predispose patients to lymphoma. This may significantly improve the success of the transplant and reduce the risk of relapse.
• Cord Blood Transplants: Research is taking place in the use of umbilical cord blood as a source of hematopoietic stem cells; this is an alternative for patients in whom a suitable adult donor cannot be found. Cord blood transplants have lower h risks of GVHD and are becoming more and more popular.

Conclusion

Allogeneic bone marrow transplantation plays a significant role in managing patients of Hodgkin and non-Hodgkin lymphoma, particularly those who have been reported to be in relapse or at high risk. Keeping in mind the difficulties and risks inherent in the transplant processes, the advancements in the transplant techniques and better support care have infused new hope by bettering the prognosis of patients with such life-threatening diseases.