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:
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.
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.
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.