Here's my take on the disease--as a 39-year-old Chinese-Irish New York male who was diagnosed with Stage IV blastic MCL on 2/24/97 after 3 weeks of spleen, lung and liver disorder. Went through several rounds of alternating methotrexate (MTX)/Ara-C and Hyper-CVAD (February through early July), removed spleen in mid-March, had an autologous peripheral blood stem cell transplant on August 1st, and have been fully active, healthy and working since 10/1. Had a full head of hair by 12/1. Was in CR after the second round of high-dose chemo. Now run 20-30 miles each week, have learned to play the piano, and am planning an adoption. Just received the first of several Hepatitis vaccinations so my wife and I can travel through Vietnam, Thailand and Cambodia.
Treatment Options:
It seems there are two schools of thought on MCL: the pessimistic and the cautiously optimistic. Both schools agree that conventional NHL therapy-i.e., CHOP alone-will not cure MCL. The reason is that there are few, if any, documented 5-year survivors of MCL who underwent CHOP therapy alone. So everyone is searching for an alternative. Thus, the two schools.
The cautiously optimistic school believes that MCL behaves more like an intermediate grade lymphoma than a low grade one, and should therefore respond to (and perhaps be cured by) a combination of dose intensification, irradiation and marrow cleansing or replacement. On the other hand, the cautiously optimistic school notes that MCL is somewhat chameleon-like-evading characterization as a pure intermediate grade lymphoma by behaving at times like a leukemia. The school therefore broadens the conventional chemotherapy cocktail (Cytoxan [aka cyclophosphamide], adriamycin [aka doxorubicin] , vincristine and prednisone or decadron) to include drugs with proven effectiveness against acute and chronic leukemias (Ara-C [or cytarabine], methotrexate, and occasionally cladribine). That's the school that developed my course of treatment: alternating cycles of Hyper-CVAD (basically, a high- dose, slow-drip version of CHOP) and MTX/Ara-C, followed by total body irradiation and an autologous BMT [aka the MD Anderson protocol].
What we know for sure is that the MD Anderson protocol and its brethren produce longer and greater numbers of complete remissions (recent results: 100% failure-free CR for first-timers with a median follow-up period of 2 years). What is unknown is whether any MCL patients have actually been cured--the trials are only 2-to-3 years old. The leading proponents of the cautiously optimistic school are, not surprisingly, institutions which have invested heavily in transplant technology: MSKCC, MD Anderson, Fred Hutchinson, the University of Nebraska, and the University of Heidelberg. Disagreements between these institutions address a wide range of important, but nevertheless subsidiary, questions: the length of chemotherapy before transplant (current wisdom: shorter is better); the risk-reward trade-off between an imperfectly matched allogeneic BMT (which can easily kill you) and an autologous BMT (which risks reinfusion of undetected diseased cells); the decision to purge (or filter) stem cell harvests using monoclonal antibodies before transplant (method not yet proven to catch everything, but destroys lots of good cells too); the amount of preparatory irradiation (MCL may find sanctuary in tissue which only radiation can get to-spinal fluid, the brain, muscles); and the intensification of dosage which the body can withstand (MSKCC is conservative, MD Anderson is aggressive).
The pessimistic school begins with the premise that MCL is sensitive to, but not eradicated by, conventional chemotherapy agents (cytoxan, adriamycin, vincristine and prednisone or decadron)--no matter what dosage. The premise is reinforced by research at Dana Farber on long-term survival of autologous versus allogeneic BMTs. First, small sample comparisons of 5-10 year survival are sobering: no long-term survivors of low grade lymphomas or MCL following autologous BMTs; versus reasonable survival rates (50%) for allogeneic BMTs. In addition, they point to PCR studies (basically, gene mapping studies looking for rearrangement of the BCL1 and IgH genes) of patients following transplant. In the case of autologous BMTs, they invariably find evidence of MRD (minimal residual disease), whereas they often do not in the case of allogeneic BMTs. I call this the pessimistic school because it says, without pathbreaking changes in the types of chemical agents used, the autologous BMT patient is essentially doomed. Critics of this school point out that Dana Farber's PCR and long-term survival research: was conducted on low grade lymphomas, not intermediate ones; excluded patients receiving anti-leukemic agents (Ara-C/MTX) in addition to standard NHL drugs; and didn't have lots of patients with truly high-dose chemotherapy.
For the pessimist, the options are fourfold: (1) improve the odds of surviving a mis-matched allogeneic BMT; (2) distill the difference between an allogeneic and autologous BMT (rejection response) into a simpler, less risky procedure (injection of chemicals known to induce organ rejection, and thus a potential graft-vs.-lymphoma [aka GVL] response); (3) develop actual MCL antibodies (IDEC and, to a lesser extent, interferon); and (4) deliver toxins more effectively (monoclonal agents like Rituxan, which bond to DNA expressing positive CD-20 genes, as many MCL cases do).
Obviously, the two schools are not mutually exclusive. And everyone is eagerly awaiting research on all four of the above options. But none of the above are perfected, and because any regimen is severe and requires a full-scale commitment, you have to choose between which path to risk first. Because the first school promised a good chance of complete remission for a lengthy period, I felt it was worth taking. Research is progressing so fast that I felt the buy-time approach made sense. Because I'm young, I might enlist in a 3-out-of-6 antigen matched allogeneic BMT (my younger brother) if I relapse. Alternatively, I may see more substantive evidence emerge that Rituxan and IDEC are effective. Those options are still available. In the end, the only thing you can depend on is that inaction and CHOP alone are highly dubious strategies.
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Here is a post Dale Pharis (another MCL patient on this list) sent about the MD Anderson protocol last October. Dale also posted a couple subsequent summaries of failure-free survival rates for first-timers with median follow- ups of 24 and 30 months, respectively, but I deleted the electronic copies. I'll send you a fax of them if you'd like.
Treatment Results with Hyper CVAD and High Dose Methotrexate/Ara-C Followed by Stem Cell Transplantation for Aggressive Mantle Cell Lymphoma
Patients with mantle cell lymphoma (MCL) of the diffuse and nodular histology have poor response to conventional chemotherapy and short survival. We investigated the use of the intensive regimen of HYPER CVAD, alternating with high-dose methotrexate/ara-C (HD MTX-ARA-C), patterned after the childhood Burkitt ALL therapy designed by Murphy et al, to reduce the tumor burden, and subsequently consolidate response in patients 65 yrs with high dose cyclophosphamide (CY) (60mg/kg/dx2), total body irradiation (TBI) (12.0 Gy in 4 fractions) and autologous or allogeneic (for patients 55 yrs) stem cell transplantation. Patients were to receive 8 cycles of 1) HYPER CVAD (CTX 300mg/m2 Q 12 hrs x 6 D1-3; VCR 2 mg D4 and 11; Adriamycin 50mg/m2 D4 and 5 (48 hour infusion); dexamethasone 40 mg D1-4 and 11-14); alternating with 2) HD MTX-ARA-C (MTX 1 g/m2 over 24 hrs D1; ARA-C 3gm/m2 over 2 hrs Q 12 hrs x 4 D2-3) [4 HYPER CVAD + 4 HD MTX-ARA-C]. 25 patients were treated (4 with the chemo arm alone because of age 65); median age 54 (range 41-75); 21 were males; 22 had diffuse MCL; one had blastic features; all had stage IV disease; 8 had B symptoms; 10 had elevated LDH; 8 patients had bulky disease of 10 cm; 24 had marrow, 7 GI and 6 peripheral blood involvement. 17 were newly diagnosed. One patient died with the first cycle of HYPER CVAD, secondary to pneumonia; he was 75 years old. 20 patients were evaluable for response after 4 cycles. 8 (40%) had CR, 11 (55%) had PR, and one had a mixed response post cycle #2 and proceeded immediately with allotransplant. 20 patients were treated with the intention of transplant; two were denied by insurance. So far, 9 have received autologous (7 with peripheral blood) and 4 allogeneic transplants. 12 achieved CR (9 were in PR post cycle #4 HYPER CVAD/HD MTX-ARA-C), and one is too early to evaluate. One patient died in CR 3 months post autotransplant secondary to interstitial pneumonitis. The remaining 12 patients are in CR with a median follow-up of 6 months (range 2 to 25) from the time of transplant. This suggests that (1)HYPER CVAD/HD MTX-ARA-C can induce high remission rates allowing autologous stem cell harvest and, (2) consolidation with high dose CY/TBI was well tolerated and was able to increase the rate of CR (cumulative CR 17/25 = 68%).
For further information concerning this treatment plan, please contact Issa Khouri, M.D. at M.D. Anderson Cancer Center, Blood and Marrow Transplantation Section (713) 794-5743, Dr. Hagop Kantarjian (713) 792-7026; or Dr. Charles Koller.
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Finally, here is a recent post by me to another patient about my doctors--if you want a second opinion:
A fellow MCL BMT patient while I was at MSKCC also was on the Sloan protocol (ICE + CHOP). His doctor was Carol Portlock, and he is now on daytime television in a leading soap opera. So forgive Sloan if they seem somewhat inflexible--they have had success.
Notwithstanding Sloan's success, I learned of the MD Anderson protocol while awaiting a splenectomy at NYU. I was dying fast and groping for answers. Found some promising preliminary results from studies at the University of Heidelberg and MD Anderson on the Internet. Both used intensified, slow-drip versions of CHOP, supplemented by anti-leukemic drugs (in Anderson's case, methotrexate and Ara-C). I made an overnight decision to give one of them a try.
Fortunately, my oncologist was a former researcher at MD Anderson. He called his former colleagues, affirmed that I was a good candidate, and switched my treatment. I did some of the chemotherapy at the clinic, some at home, some even on the road. Checked into MSKCC when I was ready for my transplant. The oncologists there were not pleased I skipped their ICE/CHOP protocol, but they didn't reject me either.
My main oncologist was Dr. Joseph C. Bottino, director of the Strang Cancer Care Clinic--now affiliated loosely with NYU. It's located downtown at 320 E. 15th St., NY, NY 10003 (212-475-6066). He's a very good (and open-minded) hematologist. So is his colleague, Dr. Lee B. Shechtman--the doctor who originally diagnosed me.
I found Dr. Bottino through my mom, who had successive bouts with ovarian, intestinal and colon cancer 7-10 years ago. Dr. Bottino's brother, Gino, was her oncologist, and saved her life. We're their star patients, so feel free to use our names--we still see them regularly.
Cytoreduced with Hyper-CVAD, alternating with high-dose methotrexate/Ara-C at 21-day intervals:
Course 1: Cyclosphosphamide 300 mg/m2 over 3 hrs Q 12 hrs x 6 doses - days 1,2,3. Doxorubicin 25 mg/m2/day IV over 24 hours daily, days 4 and 5. Vincristine 2 mg IV, days 4 and 11. Decadron 40 mgIV or P.O. daily x 4 days, days 1-4 and 11-14. G-CSF 5 micrograms/kg SQ daily starting 24 hours after end of doxorubicin infusion until ANC recovery 4 x 103.
Course 2: Methotrexate 200 mg/m2 IV over 2 hrs, then 800 mg/m2 over 22 hours on day 1 (give 12 hours after end of infusion citrovorum rescue 50 mg P.O. followed 6 hours later by 15 mg P.O.Q 6 hrs x 8 doses). Ara-C 3 gm/m2 IV over 2 hrs Q 12 hrs x 4 doses on days 2 and 3. G-CSF 5 micrograms/kg SQ daily starting 24 hours after end of Ara-C infusion until ANC recovery to 4 x 103/&m. Patients <65, 8 courses. Patients >60 years of age or patients with a serum creatinine of >1.5 mg/dL receive only 1 gm/m2 of ara-C x 4 doses.
BMT candidates: Cyclosphosphamide 60 mg/kg infused intravenously over 2 hours daily on day -7 and -6. Patients receive MESNA 10 mg/kg IVPB q 4th for 12 doses beginning 1 hour after initiation of cyclophosphamide treatment. TBI 3 Gy daily, days -4 to -1 for a total of 12 Gy. Lung shielding (6 half valve layers) performed on third dose. Day 0 stem cells infused intravenously. Autologous bone marrow and G-CSF mobilized peripheral blood cells processed by positive selection for cd-34 positive cells. G-CSF 5 mcg/kg starting day 0.
I followed the Anderson protocol for chemotherapy, but the pre-BMT induction therapy was MSKCC's regimen: similar, but supplemented by high-dose etoposide. Also, lung shielding for every dose and no purging.
But it's more complicated than that. I was told at MDAnderson that prior treatment with CHOP-like regimens makes it more difficult to achieve adequate response from future chemo to prepare for a transplant. (Unlike other indolent NHLs, MCL usually cannot be put into multiple durable remissions.)
This is the difficulty of the decision that needs to be made for initial treatment. It appears that the best chance for success with a transplant is after the first good remission. While conventional chemotherapy can extend your life, it shows no curative potential. On the other hand, transplants are still considered experimental and not enough long term data exists to know how it compares in the long run with conventional treatments.
It seems to me that if one wants to take the conventional chemo-only approach, MCL certainly should not be considered just another NHL and more rigorous regimens combining multiple chemotherapies using fractionated sequential doses should be used, like MDAnderson's hyper-CVAD, HD MTX/Ara-C. Tom
This leads me to look for alternatives. The alternatives that I am interested in are nutrition and herbal medications. Has anyone had success in these areas?
Dear Dennis, I achieved a "spontaneous regression/possible remission" and continue to do very well while following the Gerson therapy, taking Coley's mixed bacterial vaccine, and various other approaches. Whether this is in spite of, or because of, what I'm doing doesn't really matter. I eliminated toxins as much as possible from my lifestyle, eat almost exclusively organic and vegetarian, detoxify, and supplement my diet. It's been almost a year since all my nodes including a tumor the size of a plump hot dog on my neck disappeared. I follow with great interest all the newest treatments as described on this list, and even have an identical bone marrow donor match. I'll consider those treatments when I have to. Lots of promising stuff out there. I didn't have the Internet after I failed CHOP and was getting sicker. My onc didn't give my any hope, so I figured I'd have to do it my self. So far, so good. Write me if you want more details. Take care of yourself - Michele
In my case my oncologist sent me to Loyola Medical Center to review my status after three chemo. cycles. They feel that I am responding well to the treatment and I am in partial remission. They have recommended three more cycles as long as I continue to improve. They do not feel that a bone marrow transplant is appropriate for me, what a relief. They intend to follow the sixth cycle with Interferon. So I guess I'll crank up the research on Interferon. I am also using essiac but I haven’t heard of pau'd arco. Thanks again for all your help. Finding this web group is the best thing that has happened to me since I became ill. I have always been a person with a positive can do attitude, your responses have reinforced my determination. Dennis
Written by Pat Flanagan, Jeff ?, Tom ?, Michele Michuta, and Dennis Swedo.
Gathered by Vera Bradova © 1998
Updated 8-5-1998
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