MPD is a disorder that involves abnormally increased blood cell masses in the bone marrow. Therefore, it consists of polycythemia vera, essential thrombocythemia, and primary myelofibrosis group. Although several treatments are available for the management of symptoms and the control of disease progression nowadays, allogeneic BMT still remains the only potential option that might cure diseases, especially such as primary myelofibrosis.
Allogenic BMT is the replacement of the patient's disease bone marrow with healthy donor stem cells. In general, the transplantation process includes a few complex steps: a proper donor search, preparing of a recipient, a transplant, and a recovery process. BMT offers the patient an opportunity to be cured, but, at the same time, has potential complications and risks of death; therefore, such treatment may be mainly indicated for younger patients or those in a good general condition.
Find a Doctor & Schedule
Every patient with a myeloproliferative disorder who is considering an allogeneic BMT should be referred to specialized centers with comprehensive programs of transplantation. Such specialized centers, like the Blood and Marrow Transplant Program at NYU Langone's Perlmutter Cancer Center, can grant patients access to experienced teams of transplant specialists and to all the latest treatment modalities, including access to clinical trials. An initial consultation with a specialist in transplantation can be scheduled in order to allow the patient to be evaluated for the appropriateness of undergoing BMT.
Types of Myeloproliferative Disorders
MPDs are a group of disorders including several individual disorders characterized by the overproduction of one or more of the following blood cells:.Primary Myelofibrosis (PMF): A chronic, progressive disorder where bone marrow is gradually replaced with fibrous tissue, having very debilitating consequences, such as severe anemia and an enlarged spleen, amongst others. PMF has poor prognosis, and allogenic BMT is usually considered the only option for cure.
PV, on the other hand, is Polycythemia Vera; a condition of overproduction of red blood cells, resulting in the blood being thickened and leading to vast chances of clotting. Less often, BMT is made use of in the cases of PV, though it might be turned to in advanced cases or if other modalities of treatment fail.
ET: An over-abundance of platelets that can lead to thrombotic and/or bleeding complications. Like PV, BMT is seldom a chosen initial treatment, although it has been done in cases not responding to other therapies well.
Diagnosis
MPDs are diagnosed by a combination of blood and bone-marrow tests and genetic testing. Following are some tests usually considered:
- Complete Blood Count: This is a test to count the levels of different types of cells in a sample of
- blood.Bone Marrow Biopsy: The bone marrow is examined under the microscope to check the count and the appearance of cells.
- Genetic Testing: It detects mutations, like JAK2, CALR, or MPL gene mutations, which are usually associated with MPDs.
An accurate diagnosis is very important in deciding appropriate treatment and determining whether BMT may be helpful to a patient.
Medication
MPDs are usually initially treated with drugs to alleviate symptoms and reduce the progression of the disease. Drugs commonly used for this purpose include :
- Hydroxyurea: Reduces blood cell production, primarily in PV and ET.
- JAK Inhibitors- eg Ruxolitinib: Targets specific genetic mutations driving the disease process, mostly in MF
- Interferon: It is an immunomodulator and may be used in younger patients or in an individual who expects BMT down the line.
- Aspirin: Can be used to prevent blood clotting in PV and ET.
Even though these drugs frequently reduce the symptoms, improve the quality of life, they are not curative; thus, BMT is discussed with patients with advanced or high-risk disease.
Blood Treatments
Apart from drugs, various forms of blood treatments are used when managing and treating symptoms of MPDs:
- Phlebotomy: This is the removal of blood regularly from the body to reduce the number of red blood cells. Mainly performed in PV.
- Blood Transfusions: Given in the setting of myelofibrosis to correct anemia and sustain the red blood cell burden.
- Platelet-Lowering Therapy: Administered to bring down the platelet count in patients with ET and PV at a low risk of developing blood clots and bleeding.
These are supportive strategies that sustain safe levels of one's blood counts, usually having other strategies done simultaneously. Stem Cell Transplantation
Stem cell transplantation is a cornerstone of potentially curative treatment in selected MPDs, particularly myelofibrosis. The procedure involves harvesting stem cells from a suitable donor and then transplanting these cells into the patient after a conditioning regimen. The critical stages of this process include:
- CONDITIONING: Formerly, this term was used to describe how high doses of chemotherapy—with or without radiation—were critically given to kill the patient's diseased bone marrow to make room for receiving new, healthy stem cells and lessen the possibility of rejection of the donor's cells by the patient's immune system.
- Stem Cell Infusion: Following this step, healthy donor stem cells are infused into the patient's bloodstream. After infusion, the cells travel down arteries into the bone marrow to begin making new blood cells, gradually replacing the dysfunctional marrow with new, fully functioning cells.
- Engraftment and Recovery: The transplanted stem cells must engraft, or take hold, in the patient's bone marrow and start to produce healthy blood cells. This process takes several weeks and is closely monitored through blood tests and clinical observation.
The Search for a Stem Cell Donor
The primary determinant of successful allogeneic blast marrow transplantation is an adequate stem cells donor.
- Compatibility Criteria: The human leukocyte antigens (HLAs) are the proteins on the surface of the cells responsible for the primary role in the working of the immune.
- Siblings as donors: The probability of the match from siblings is even more perfect, where 25% was of the same type.
- Unrelated Donors: If a sibling match is not available, the transplant team can search national and international bone marrow registries to find a matching HLA type from an unrelated donor.
- Haploidentical Transplantation: If no perfect match is found, a partially matched donor, usually a haploidentical parent or child, may be utilized. In this approach, extra treatments are essential for preventing rejection and lowering the risk of graft-versus-host disease.
This process may take several weeks to even months, and during this time, patients are usually given other treatments to manage their disease.
Collection and Transplantation of the Stem Cells
Once a compatible donor is obtained, there are two most common techniques to collect the stem cells:
- Peripheral blood stem cell collection: This process is far more common. The donor is treated with a medication that stimulates the bone marrow to release its stem cells into the bloodstream. Blood is then drawn from the donor and processed by a machine known as an apheresis device; it removes the stem cells and returns the rest of the blood to the donor.
- Bone Marrow Harvest: This is less frequently done and is basically done by harvesting stem cells from bone marrow, especially the pelvic bone, through a needle and a syringe. The patient may require anesthesia, and often multiple piercings of the marrow are needed to collect an adequate number of stem cells.
After collection, the cells are processed, preserved, and stored for future infusion into the particular patient at the time of transplantation.
Recovery from Stem Cell Transplantation
BMT reversal is a long-term process requiring full concentration and carefulness:
- Lengths of stay: Patients may be put under hospitalization for three to four weeks immediately after the transplantation is done. All the time, a patient will be kept in an isolation room that is highly sterilized to limit the amount of infection. This is mainly because the patient's immunity is greatly weakened.
- Monitoring for Complications: Infections, bleeding, and GVHD are common complications during the recovery phase, the ones that are combated using prophylactic antibiotics and other medications. Blood transfusions may be needed in order to support the patient until the new stem cells begin producing adequate blood cells.
- Engraftment: This important phase called engraftment usually occurs in two to four weeks after transplant and is characterized by a steady rise in the patient's blood cell count. Engraftment success reflects the fact that new bone marrow is working well.
- Long-term Recovery: Full recovery may take several months to a year. Patients require routine follow-up visits, blood tests, and even bone marrow biopsies in the day to watch the effectiveness of their transplant. Additionally, another reason for follow-up is that it helps the doctors get early signs of relapse or late effects of complications.
Support
Support becomes an important part of the treatment as the patient's ordeal is not only physical but also psychological:
- Psychological Support: It has effects on a patient's psychology, including anxiety and depression, with treatment being of high intensity and the recovery period taking a long. Counseling support groups could, therefore, be made available for the patients.
- Nutritional Support: Proper nutrients are required during recovery; thus, dieticians and nutritionists can help in maintaining good nutrition by controlling several side effects such as nausea and mouth sores, which are common after high-dose chemotherapy.
- Mental Caregiver Support: Patients and caregivers require an extended level of support as the patient continues with recovery. Several caregiver support groups and resources may provide valuable help and counseling.
Other Resources
Several resources are available for patients and caregivers in a BMT journey:
As well, most cancer centers provide booklets, online preparation and educational classes for patients and families about their BMT process, possible side effects from the process, and advice on recovery. Financial Aid BMT is without doubt highly costly, and virtually all patients require some level of financial support to put up with the cost associated with BMT, hospitalization, and after-care. The transplant hospital's team of financial counselors may help determine sources of coverage through insurance, grants, and other forms of financial aid.
Support Groups: Joining a support group, whether in person or online, will provide emotional support and practical advice from others who have gone through similar experiences.
Clinical Trials
Clinical trials offer access to new treatments and state-of-the-art strategies that may offer better outcomes for the BMT patient. For patients with serious diseases and for those with forms of the disease that do not respond well to standard treatment, enrollment in a clinical trial is a recommended option. All patients should discuss with their transplant team the access to and appropriateness of clinical trials.
Conclusion
Allogeneic bone marrow transplantation is considered a potentially curative treatment in patients with primary myelofibrosis, among other myeloproliferative disorders. Very complex, with significant risk associated, it offers many patients their best chance at long-term survival and a cure. It is through careful planning, support, and access to specialist care that a patient undergoing BMT will negotiate the many challenges in the procedure, in order to help assure a good recovery.
Any individual planning to undergo a BMT should be referred to a specialized transplant team, where he or she will have the opportunity to review treatment options and know all about participation in clinical trials. Although the path of BMT is tortuous, with appropriate care and support, patients can have a positive outcome and improved quality of life at the end.
