The Non-Hodgkins Lymphomas are a diverse group of cancers arising out of the lymph nodes. These diseases include some of the slowest growing tumors to some of the fastest growing human cancers. Many patients first notice their disease when to feel a swollen lymph node or develop fevers, night sweats or weight loss.The most important factor in determining prognosis and treatment is obtaining an accurate diagnosis. There are many different types of lymphoma. Examination of the biopsy under the microscope or with additional studies (such as chromosome studies or flow cytometry) should help clarify the subtype of lymphoma. Although there are over 20 different types, these can usually be divided into the "low grade" tumors , "intermediate grade" tumors and the "high grade" tumors.
Aggressive Lymphomas (Intermediate and High Grade)
These subtypes of lymphoma are characterized by rapid growth. If left untreated, the prognosis is very poor. However, many patients with the aggressive lymphomas are curable with modern chemotherapy.
Intermediate grade lymphomas are usually treated with combination chemotherapy such as CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone). Depending on the stage of disease (how localized or spread the disease is), the age and overall health of the patient, the serum LDH (a marker of tumor burden) and the presence of symptoms, cure rates for these types of lymphoma may vary between 20 and 50%.
High-grade lymphomas (including Burkitt's lymphoma and Lymphoblastic lymphoma) are very aggressive. These are usually treated with highly complex chemotherapy regimens spanning many weeks. Some require treatment similar to that given to patients with acute leukemia. Many of these patients will be offered bone marrow transplantation early in their treatment.
Transplantation for Aggressive Lymphomas
As noted above, many patients with High-grade lymphomas will be offered transplantation as part of the initial treatment of their disease. For example Santini et al (Ann Oncol 1991; 2: Suppl 2: 181) reported a 50% continuous remission rate for patients treated with early transplantation for lymphoblastic lymphoma.
High-dose therapy with transplantation plays an important role in the treatment of aggressive lymphomas that have relapsed/recurred following initial therapy. The PARMA trial (New England Journal of Medicine 1995; 333:1540) has documented superiority of transplantation compared to standard-dose therapy in patients with first relapse intermediate grade disease. In this important study patients who had a recurrence of their disease received two cycles of standard chemotherapy. Responding patients were then given either additional standard chemotherapy or a transplant. At 5 years more patients who received a transplant were still in remission (46%) compared to patients receiving standard chemotherapy (only 12%). This important study has changed the management of relapsed lymphoma and made consideration of transplantation at the time of first relapse very commonplace.
Based on the results of transplantation after relapse, several investigators have begun to explore the role of this therapy as part of the initial treatment of patients with high-risk intermediate grade disease. Haioun et al (J Clinical Oncology 1994; 12:2543) treated 462 patients with high-risk lymphoma with initial chemotherapy followed by either transplantation or more chemotherapy. Both groups received more chemotherapy than is commonplace. In the initial report both treatments appeared to do equally well. However, in a recent update of the subgroup of patients with poor prognostic features (Shipp risk factors), the transplant treatment has been noted to yield superior results.
The Adult Stem Cell- Bone Marrow Transplant Program of Hackensack University Medical Center has active transplant treatment protocols for Aggressive Non-Hodgkin’s Lymphomas. For more information on this treatment or to schedule an appointment call (201) 996-5849.
AUTOLOGOUS TRANSPLANT OPTIONS
High-dose treatments with BCNU, etoposide, cytarabine, and cyclophosphamide (BVAC) rescued by autologous peripheral blood stem cells can be curative in patients with relapsed or refractory non-Hodgkin’s lymphoma. Patients with marrow involvement by disease may also benefit from tumor purging of the autologous peripheral blood stem cells in our stem cell laboratory. We are currently offering patients "positive" selection techniques using a CD34 column. Post-transplantation interleukin-2 infusions may also be used to reduce recurrence rates. For more information on our stem cell selection methods, check out the stem cell laboratory section.
The Hackensack University Medical Center’s Adult Transplant Program is also participating in a national Eastern Cooperative Oncology Group trial comparing standard dose chemotherapy (CHOP) with sequential high-dose transplantation therapy in newly diagnosed patients with "high-risk" lymphoma. For more information click here.
ALLOGENEIC TRANSPLANT OPTIONS
For patients with Tissue-matched (HLA-matched) brother/sister bone marrow donors allogeneic transplantation treatment protocols may be appropriate. One trial uses high-dose cyclophosphamide combined with either total body irradiation or high-dose busulfan. Following this aggressive conditioning therapy, bone marrow (or peripheral blood stem cells) from an HLA-matched donor is infused. Graft-versus-host disease prevention is accomplished with combinations of tacrolimus and methotrexate. This very aggressive curative treatment requires a one-month hospitalization.
UNRELATED TRANSPLANT TREATMENT OPTIONS
For patients lacking a family member marrow donor, the Hackensack University Medical Center Transplant Programs are participating in several unrelated transplant protocols. The National Marrow Donor Program has enlisted over 3 million volunteer bone marrow donors. If an HLA matched unrelated donor can be located, a transplant using high-dose cyclophosphamide and total body irradiation can be performed.
Hackensack University Medical Center is also participating in a multicenter trial evaluating the use of expanded Cord Blood Cells in the treatment of cancers and blood diseases. This trial also extends the treatment options for patients without HLA Matched relative donors. For more information click here and also review ex-vivo expansion in the stem cell laboratory section.
Low Grade Lymphoma
The low-grade tumors are very slow growing, and patients frequently live more than 7-10 years with their disease. Treatment is generally aimed at controlling the symptoms of the disease, rather than attempting to cure the disease. Treatments such as "watchful waiting", chlorambucil, cyclophosphamide, prednisone, interferon, monoclonal antibodies and fludarabine may be appropriate.
Role of transplantation in low grade disease
Although most patients live for many years with low-grade lymphomas (also known as indolent lymphomas), the above mentioned treatments are not curative. In the "young" patient with low grade lymphoma aggressive treatment including bone marrow transplantation may offer a chance at longer survival. This treatment is still relatively new for this disease. Three recent studies have shown promising results in this subtype of lymphoma. A report from Nebraska (Bierman P et al: Proc Am Soc Clin Oncol 1996:15:415) in 100 patients with advanced disease yielded 67% survival and 48% continuous remissions with high-dose treatment at 2.7-years. In patients with recurrent or refractory disease, investigators in London (Rohatiner AZS et al: J Clinical Oncology 1994;12:1177) obtained 92% survival and 55% continuous remissions at 3-years follow-up with transplantation. Similarly, investigators in Boston (Freedman A et al: Blood 1991; 77: 2524) treated patients with advanced disease with autologous transplantation and noted over half of the patients treated with transplantation remaining alive after 2 years.
These encouraging results in patients with recurrent and refractory disease have led to several trials in patients with newly diagnosed disease. One trial of early transplantation has yielded 90% survival and 65% disease-free survival at 24 months of follow-up (Freedman A et al: Blood 1993: 82:supplement 1: abstract 1313).
The Adult Stem Cell- Bone Marrow Transplant Program of Hackensack University Medical Center has active transplant treatment protocols for Low Grade Non-Hodgkin’s Lymphomas. . For more information on this treatment or to schedule an appointment call (201) 996-5849.
ALLOGENEIC TRANSPLANT OPTIONS
For patients with Tissue-matched (HLA-matched) brother/sister bone marrow donors allogeneic transplantation treatment protocols may be appropriate. One trial uses high-dose cyclophosphamide combined with either total body irradiation or high-dose busulfan. Following this aggressive conditioning therapy, bone marrow (or peripheral blood stem cells) from an HLA-matched donor is infused. Graft-versus-host disease prevention is accomplished with combinations of tacrolimus and methotrexate. This very aggressive curative treatment requires a one-month hospitalization.
UNRELATED TRANSPLANT TREATMENT OPTIONS
For patients lacking a family member marrow donor, the Hackensack University Medical Center Transplant Programs are participating in several unrelated transplant protocols.
The National Marrow Donor Program has enlisted over 3 million volunteer bone marrow donors. If an HLA matched unrelated donor can be located, a transplant using high-dose cyclophosphamide and total body irradiation can be performed.
Hackensack University Medical Center is also participating in a multicenter trial evaluating the use of expanded Cord Blood Cells in the treatment of cancers and blood diseases. This trial also extends the treatment options for patients without HLA Matched relative donors. For more information click here and also review ex-vivo expansion in the stem cell laboratory section.
AUTOLOGOUS TRANSPLANT OPTIONS
High-dose treatments with autologous stem cell rescue are under development. For more information on autologous transplant options call (201) 996-5849.
NON-TRANSPLANT OPTIONS
In addition to the above transplantation trials, the physicians of the Northern New Jersey Cancer Center have expertise in the diagnosis and treatment of these diseases. Other research studies include:
1.
- Topotecan 21-day infusion in previously treated large cell lymphoma 2.
- Phase III trial of CHOP versus CHOP plus IDEC C2B8 in older patients with diffuse, mixed large cell and immunoblastic lymphoma
Call (201) 996-5800 for more information on these trials.
