Richter’s Transformation
We don’t quite know why or how it happens. But in a certain percentage of patients, their erstwhile indolent CLL suddenly morphs into a far more aggressive disease, a fast growing and far more dangerous lymphoma. The classical therapy for such patients used to be CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). Now the standard of care is R-CHOP (R for Rituxan). There is a lot of clinical evidence that R-CHOP gets far better responses and remissions than plain old CHOP, making this scary transformation a lot less dangerous.
Nevertheless, for most patients this transformation comes as a totally unexpected bolt from the blue. There is a growing concern that combination of alkylating agents and purine analogs (as in cyclophosphamide and fludarabine, for example) increase the risk of Richter’s transformation. Some research published by M. D. Anderson raises the possibility that prior history of mononucleosis (“glandular fever”) may increase risk of subsequent Richter’s transformation. There is still a lot of research that needs to be done before we can hope to understand all the underlying risk factors.
Many of you know Diane Mackinnon as our patient advocate on the FDA drug advisory panel. She is also a dear friend of mine. Last year she joined the ranks of CLL patients whose disease underwent Richter’s transformation. I am delighted to tell you Diane is doing well right now. Below is her story. We are all stronger when our members share their experiences with the rest of the patient community. Please join me in wishing her continued good health.
Notes from a Richter’s Transformation Survivor
I have discussed my Richter’s transformation with Chaya extensively which lead to her suggestion that I write up my experience. First I recommend reading her excellent overview of Richter’s transformation to provide context for my saga:
Background
At age 58 in 1997 I was diagnosed with stage 0 CLL and subsequently followed by an NIH study and a local hem-onc. No history of mononucleosis or other EBV exposure. I had a 13q deletion (good) but high cd38 and unmutated IgVH (not good). My lymphocyte doubling time was about 13 months so within 5 years I needed treatment; marrow impacted, spleen enlarged, adenopathy, and blood counts, other than WBC at 256k, trending down. I was and continue to be under the care of Dr. Bruce Cheson at Lombardi Cancer Center, Washington DC. 1st treatment was 6 cycles Fludara/Rituxan (FR) Jan 2003 which gave me a good nPR which lasted four years. 2nd treatment, this time with a mediport for infusions and blood tests, was a repeat of FR which again gave me a good PR but not the sought after CR. In 2009 I started periodic IVIG as IGg was falling below 300. I was stable until October 2009 when my counts all crashed precipitously. 3rd treatment was 6 cycles Bendamustine/Rituxan which was difficult each week after treatment (nausea and fatigue) but again provided a good PR after which I felt great. Up until this point I had managed my disease and treatment with minimal impact on my husband (other than psychological) since being an independent cuss I prefer to do it myself. That approach would soon become impossible.
Transformation onset
Spring of 2011 I experienced gastrointestinal upsets which were consistent with my history of Irritable Bowel Syndrome (IBS) but more troublesome. I coincidently had a colonoscopy for which I was due; it came back clear. I saw Dr. Cheson in May with no obvious problems. In June I started to feel lousy, fatigue, periodic fevers, very bloated stomach, low appetite. It all happened rather quickly with my initial symptoms masked by my IBS problems. Dr. Cheson advised going to the ER for admission. They were quite responsive: Chest x-ray, CT scan abdomen, echo cardiogram, BMB, EKG, ultrasound of abdomen indicating greatly increased nodes and fluid drain of acites in abdomen. Lots of blood tests of course with low platelets and high LDH. Within 2 days the diagnosis was made of Richter’s transformation into aggressive Diffuse Large B Cell Lymphoma (DLBCL). I knew that was a bad turn of events (survival 5-8 months) so I immediately agreed to the gold standard protocol of R-CHOP which was initiated on the third day.
Treatment Cycle 1
I was inpatient for Cycle 1 on June 24, 2011. I was given IV Rituxan, cyclophosphamide (cytoxan), vincristine (oncovin) and doxorubicin (adriamycin which is cardiotoxic)) on day 1 and oral prednisone for days 1-5. I was also given a new drug rasbericase to help prevent Tumor Lysis Syndrome (TLS) as well as allopurinol and Claritin (as opposed to Benedryl to which I am over sensitive) premeds. Those days in the hospital are a bit of a blur but I do remember 2 nights when I had hallucinations during which I could not tell dreams from reality for a few hours. My husband visited daily, my daughter came after work each day and my son flew in from Boston for 4 days. I was finally discharged on June 27, day 4. I had to come back on day 5 outpatient for a Neulasta injection to control neutropenia. (Could not be done while I was hospitalized due to Medicare rules which allow only Neupogen for inpatient). I was sent home with a variety of oral medications: allopurinol for TLS (2 times a day), prednisone for last cycle day, zofran for nausea every 8 hours, metroprolol to prevent hypertension, protonix to prevent ulcers, compazine for nausea every 6 hours, and percocet for pain (used seldom). I was a walking pharmacy and felt awful. My son made up a spreadsheet for the medication schedule. My children and husband were devoted but terrified caregivers.
July 1, I was back in the hospital with febrile (102F) neutropenia. Given neupogen injections and IV cefeprin antibiotic. July 3 given 2 units red blood cells as hemoglobin was down to 7.5 and the addition of vancomycin antibiotic. Fever finally broke so I was discharged after yet another scary inpatient week.
2nd, 3rd and 4th cycles
One day every three weeks were outpatient followed by Neulasta injection Day 2. I went in for blood tests each week. I was miserable most of the time, barely fighting off nausea/vomiting with two medications (Zofran and Compazine), impressive fatigue, loss of hair, weight loss of 15 pounds. My daughter insisted on keeping me company on the infusion days.
Aug 31 – admitted via ER for high fever. Given chest x-ray, EKG, 2 units red blood. Continued spiking fever and neutropenia. Given IV cefepine and vancomycin. Sep 3 fever breaks but platelets were way down at 21. Heard later that there was a high level of concern for my condition … me too. Platelets rebound enough to discharge me on Sep 6 with prescriptions for cefdinir at 300mg twice a day for 7 days and ciproflaxin at 500mg for 10 days. There must have been no bacteria alive in me after that regimen. Fortunately I did not get diarrhea or a yeast infection from all those antibiotics.
When I next saw Dr. Cheson he noted that I was seriously struggling with the regimen and that 2 more cycles with incremental gain were not worth the real risk to my health so we stopped after 4 cycles. I was relieved to stop but of course also concerned that we had stopped short of the standard recommended 6 cycles. CT scan showed marked improvement and BMB indicated no Richter’s in the marrow (it is in the lymph nodes and usually not in the marrow) with 30% CLL involvement. Not clear how well I had responded. As a hedge, I entered a clinical trial at Lombardi for both DLBCL (Richter’s transforms into this) and CLL patients. I qualified on both counts.
In October my ENT discovered a sinus infection for which he prescribed Augmentin and nasal spray. Cough which I had for months (nobody could hear any lung involvement) continued. CT scan report mentioned something on right lung so I see my pulmonologist. He takes a chest x-ray which he compares to a previous one. Definite pneumonia diagnosis. End up on 750mg Levaquin for 10 days then 5 days more before x-ray determined infiltrate was resolved. Was almost hospitalized again but I resisted. Note to patients to be forewarned: only symptom was coughing, nobody ever could actually hear this pneumonia, no high fever, it was apparent only on the x-ray.
Clinical trial
Infusions of Rituxan and DCDT2980s experimental drug every 3 weeks. Neutropenia was the only bad side effect which was controlled by Neulasta. My platelets took a bit of a hit but remained above 50 and rebounded each cycle. An easy regimen all things considered. After 8 cycles a CT scan indicated an increase in adenopathy, i.e. some disease progression, so I had to leave the trial in April. Not clear what effect the trial drug had. Good news was that a PET scan Feb 29, requested by me with Dr. Cheson’s concurrence, indicated no active DLBCL disease. It would have been nice to have this test earlier but there may have been a medical reason to delay.
My nursing care at Georgetown University Hospital was excellent. Since it is a teaching hospital I did have to deal with some inexperienced stressed out post residency fellows which was mainly just an annoyance. That hospital has a terrific special unit (2 Bles) for immune compromised patients. The unit is sealed off from the hospital with an airlock and has a special air filtration system; each patient has a single room with bath and a lower nurse to patient ratio. All nurses on the unit are infusion certified and oncology trained. Hospitals are by definition stressful, replete with miscommunication where nothing happens when or exactly how they tell you but at least everyone was pleasant, competent and concerned with my care.
So I seem to have dodged the Richter’s transformation bullet. I have not bounced back to my pre-Richter’s level of energy and well being but Dr. Cheson was clearly pleased with the PET results. I am functional on a day-to-day basis but cannot handle exertion such as hikes or much stair climbing. I still have CLL which may need treatment again in the near future. Will I have another Richter’s transformation? I have not asked that question because I am certain nobody really knows. Grueling as my experience was it ought to give hope to any other patient who has a Richter’s transformation.
19 comments on "Notes from a Richter’s Transformation Survivor"
Thank you so much for sharing. I also developed richters transformation discovered during my last round of FCR at the age of 58. I had established a relationship with M.D. Anderson due to my 17p deletion and 4 other abnormalities and I knew I would need a MUD transplant eventually. With the new diagnosis things were put into action for some intense chemo to prep for stem cell I had my transplant on August 12 and all things considered It went pretty well. Life is different, it is an endless road to recovery, but I am here, learning to accept my limitations The Richter’s is gone according to my last check-up as was the CLL. I find out more when I return to m.d. in early June.
You are an inspiration and the only person I have heard about that handled the transformation in a different manner and with success. Keep up the good work. I must add that Chaya’ s website was invaluable to me and her personal input priceless. Thank you both for helping me and others challenged by this rare disease. Be Well, Sarah
To Sarah: Just to add, I did not really consider(nor did Dr. Cheson)the option of a stem cell transplant given my age of 72 when I transformed. That I realize is the best solution for younger patients and I am glad you have had success. May you continue to prosper.
Diane
Diane, congratulations and continued success to a woman of great determination. You will say you had no choice but you persisted through what would have proven much too daunting to some others! I think patients like you must also give doctors great incentive for pushing forward with research despite the dark areas it sometimes takes patients to.
I was dx’d 1 year after you, also at age 58. Following my first cycle of treatment, my disease always shows up as adenopathy rather than high counts. Did anyone mention to you whether patients like me are more prone to be among that very small percentage who undergo the transformation? Best-Ellen D.
Diane–Thank you for an informative and clear article. I don’t plan to undergo your treatment, but your story equips me for forging on if I do.
Ellen: Nobody I have encountered is willing to go on record with any causal relationship for Richter’s or even a statistical coincidence. Unfortunately the percentage of CLL patients with this transformation is rising. The answer from Dr. Cheson, who to his credit can admit that sometimes he does not know, would be “there is no real data on that”. We live with uncertainty constantly, don’t we? Glad to hear that you are still active after 14 years with this disease.
Best, Diane
You really are a trooper. I thought you were 58 now and just realized that was 1997. It is great to hear about the success of another way to beat Richters as their aren’t many proven success’s. You inspire me to keep up the fight.
My best,
Sarah
Good on you, Diane! You sound like the perfect person to have as our patient advocate on the FDA drug advisory panel – courageous, intelligent and realistic. Thanks for sharing your experience, and thanks to Chaya for bringing it to us.
Best wishes,
Rick
Thanks for sharing your story. While almost always with CLL you have time to consider your plan of action, you remind us that sometimes such s with RT, you need to more fast.
Stay strong
Brian
Diane, thank you for sharing your story with us. It’s moving.
My father in law has CLL and I regularly visit CLL Topics for encouragement, details and study results that I can share with him and the family. It’s first-hand accounts like this, Diana, and Chaya’s phenomenal day-to-day work that have consistently reassured and inspired us that the light shines brightly at the end of the tunnel.
Thanks again and best of luck,
Steve
It takes a tough lady to endure such a path…and I do not mean just physically. Talk about “True Grit”. Pray very very few of us need your strength…but that all of us can have some of your courage rub off.
Diane,
Thank you for sharing your personal story.
It was quite a journey.
Many blessings to you and Chaya for bringing it to us.
Rita
Diane, I guess it is true that God writes in croked lines
Thank you for sharing what you have had to endore.
I’m back in the hospital after being taken
Off cal101 march 28, I have been having the night sweats chills no fever but a lot of diarrhea
All the scope colon and endo just show colitis. I had a bowel resection in September pieces back fe that very well. This bowel problem with no clear signs has my MD here @ NYPresbyyrtian Weil Cornell medical center sum what puzzled. I too have what seems to be clean
Chest yet I’m putting put some nasty green stuff
Oh well this too will pass. My prayers and thought of all that is good and peaceful go put to all who put up with this annoyance called CLL
Tim
Pro
Diane, thank you for your story of courage, persistence and determination. You are obviously a very special lady!!!!
Your Richter’s transformation/DLBCL journey is an inspiration to all of us trying our best to live with CLL.
Bless you for being such a positive example and sharing your experience, strength and hope with our CLL patient community.
Warm regards – Patti Kruse
Thank you Chaya and Diane to share this story of courage. Happy Diane is doing well.The best to her.
Diane,
I have always admired and been grateful for your advocacy on behalf of CLL. I am so sorry you had this transformation but your story is inspiring. Please stay well. I am rooting for you.
This is a very inspiring story. My father has suffering from Richter’s Transformation. I will share this with him. I have written the progress of my father below;
My father had CLL since 1993 and now (on May-2012) he has been diagnosed as Richter’s transformation. On 30-31 of May his R-CHOP treatment has started. During the first cycle because of fever (it was 37.5oC) they stopped giving R to him, and next day they have given CHOP without any problem. We really questioned that why they didn’t complete the R treatment but couldn’t get a satisfactory answer. He was allowed to go to home same day w/o any preventive treatment or any kind of medicine such as antibiotics. Next week wednesday his fever increased and we went back to the hospital. Finally on Sunday he is transferred to the intensive care unit in the hospital because of neutropenia. He stayed there for 14 days because of very serios lung and breath problems caused by pneumonia. Now he is in the hematology section in the same hospital. After increasing his blood levels his 2nd therapy CT will start. The total CT cycle has been planned as 4. He is 66 years old. I do really feel that there are gaps and uncertainties in his treatment.
Thankyou for providing an article that provides some insight into treatment options and some hope for RT sufferers. Every article you read on the net about RS is negative.
My father at 63 was diagnosed with CLL, the chemo treatment was going well the CLL was at a manageable level. Just over one year on (last Friday)he has been diagnsed with Richter Transformation. This news has brought a shadow over the light of hope we have.
The thing that really annoys me is that he developed a 1.5cm tumour in his lymph node 8 weeks ago (14 November), he saw a stand in heamatologist (his normal doctor is on maternity leave) as soon as the tumour was noticed. The doctor said it was normal nothing to worry about yet, but to keep an eye on the growth of the tumour and any other symptoms such as night sweats, fatigue etc. Within 4 weeks the tumour had grown ten times the size to 15 cm when we contacted the doctor she said it will be ok and that she will see my dad on the 8th of January and that there was nothing she could do because the hospital was on skeleton staff.
When my dad finally saw his doctor they arranged all the usual tests and discovered the growth was in fact RT and that they must start treatment straight away.
He is in surgery at the moment having his lymph node taken out, and treatment will start on Friday.
I would love to hear back from people that have RS and to find out their experience with different treatment options.
God bless you all.
Hi, there have not been many posts lately. My Mom is in her 5th treatment cycle for Richters and looking for other stories, what is next after the 6th treatment? Any other contact info? ccollins310@cox.net
Someone recently requested that I update my current status so here goes. I am two years out with no recurrence of Richter’s. I still have CLL of course. I am currently in the NIH clinical trial for ibrutinib. After 15 months I am stable with only my low platelets in the abnormal range. I have no side effects to complain about and I feel pretty good for a 74 year old who has been through a lot of treatment. Just returned from two weeks in Budapest and Prague with my husband. SO far so good is my mantra.
Best to you all, Diane MacKinnon
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