Back Home Next

Ebbe R. Skov


Mission Viejo, CA;

1936 / Class of '99 / Type: Kappa LC / Mini-allo + relapse / Updated: 11/04

BACKGROUND: I was born 7/31/1936 and educated in Denmark as a chemist and chemical engineer [1960]. My first 20 years of work was in the chemical industry in R&D, plant operations and engineering, with periodic exposures to a large number of chemicals used in plastics, synthetic resins, lubricants, fine chemicals and petrochemicals. Long term assignments were in Brazil, Puerto Rico, New Jersey, Texas and California, and I have probably therefore been exposed to most viruses and bacteria found in Europe, North and South America. However, except for hepatitis, mononucleosis and dengue I have not had any unusual infections I am aware of and generally my health has been very good.

MYELOMA DIAGNOSIS: My first encounter with MM was at age 62 in late 1998 when I experienced pronounced night sweats several times a week, frothing of the urine caused by protein excretion. In November I had a painful rib fracture [caused by a single sneeze while driving] that my physician X-rayed without finding anything. My MM diagnosis was made four months later in March 1999 based on the development of a plasmacytoma [3 x 10-cm tumor] on my 9th rib, broken clavicle and 8 bone lesions. Bone marrow biopsy [BMB] showed 9% plasma M-cells and kappa light chain secretion [but no monoclonal Ig abnormality was detected]. My family physician turned me over to the local oncology clinic for additional testing and treatment and a month went by during which pain developed at the lower back and several of the ribs. [In hindsight it is clear that the MM progression was fairly fast, but with no Ig-secretion to alert us and no reliable light-chain assay or PET scan available nobody had a clue, and the oncologist informed me that MM usually is a slow moving disease]. The emotional impact of the diagnosis on me and my wife and two married sons was considerable in view of the then known to be a very limited survival lifespan. However, as I learned more about MM from the IMF and other patients and started looking at the various treatments as personal challenges, it helped me to channel my feelings of uncertainty and fear into a series of personal challenges and project goals.

PHASE I TREATMENT: First-line treatment was radiation [~4400 cGr] to the 9th-rib plasmacytoma over a 28-day period, a painless procedure of a few minutes duration each weekday. It was followed by 5 cycles VAD [May – October] performed with a strap-on pump for four days a month at home in Mission Viejo, CA. Monthly Aredia 90-mg infusion was started in April 1999. I had a permanent catheter [Port-o-cath] installed surgically near the left clavicle to facilitate infusions and injections, and it has remained a very useful tool for over 5 years. In mid June my clavicle broke and received two weeks radiation. Complete remission [CR] was confirmed in October 1999 by normal plasma cell count in BMB and the absence of monoclonal Ig in serum and normal blood and urine. The VAD cycle was an interesting experience due to the mood swings caused by the Dexamethasone that made me unexpectedly emotional, and I was indeed fortunate that the monthly immune system depression did not cause any infections in my case. The emotional support of my near family and friends was wonderful and completely compensated for the sense of hardship due to the chemotherapy.

PHASE II TREATMENT: Although I was in CR in October 1999, as a LC-kappa secretor I was concerned about the difficulty of monitoring MM in the absence of Ig-secretion in my case [remember that FLC assay was not available then]. I realized that MM usually revisits some time after VAD treatment, and I really did not want to wait for bone-pain and lesions as my only signal of MM progression. For this reason my oncologist then suggested a second line of treatment. He referred me to City-of-Hope Medical Center, Duarte, CA where I was tested and accepted into an experimental test protocol for “tandem auto-mini-allo BMT” in early 2000. One of my two brothers was a perfect donor match [100% 6/6 match of the major HLAs]. In March I received the autologous PSCT with ablative HDT at COH. The procedure went well and without complications, and recovery was 75% within 2 weeks, 100% within 8 weeks. We stayed at COH during the first week and actually it was “a walk in the park” except for the nausea and tiredness during that first week. The staff at COH trained my “caretaker” [wife] in all aspects of the procedures so she could help maintaining the treatment whever possible, which added to our confidence and comfort. And the incredibly competent and cheerful staff at COH helped me through what otherwise could have been a tedious journey and transformed it instead into a unique and very interesting experience.

The first transplant was followed 90 days later by mini-allo-BMT [would have been PSC except the donor’s PSC draw was insufficient]. The mini-allo-BMT had low level full-body radiation and less severe chemotherapy than the previous autologus SCT and the recovery was uneventful with a minimum show of graft-versus-host-disease [GVHD] in the mouth and digestive tract. Low level GVHD is desirable to act against the MM cells, however the risk of severe GVHD is a concern [it can kill the patient]. During the first 3 months the bone marrow recovered, my blood type changed 100% from type “O” to my brother’s “A”, and the immunodepressant chemo was decreased very carefully and stepwise to zero. [We discovered four years later that although the “chimerism” was 100% according to DNA testing the T-cell subgroup showed that only 92% were “my brother’s cell type and 8% were “mine”. This coexistence is not entirely uncommon I’m told, however it suggests how “a few” other host-cells such as B-cells and MM-cells also can escape the mini-allo-BMT procedure and adapt to coexist with the donor blood system, and later cause a MM relapse.

Aredia infusion was continued monthly except for three 4 – 8-week delays due to elevated serum creatinine above the normal range. During 2003 I tried substituting Zometa [2 mg/monthly], however we discontinued because the creatinine level increased above normal limit within 4 months. At the time we were advised that kidney impact from bisphosphonates seemed to be less reversible with Zometa than Aredia, so I went back to Aredia [90 mg/monthly]. The principal reason for continuing Aredia was to help strengthen the bones, yet it was also seen as a “preventive” measure in case of relapse [and in retrospect a justified idea]. Monitoring was confirmed at COH every 4 – 6 months January 2000 – June 2004 by checking BMB, serum proteins, Ig-electrophoresis and 24-h urine BJ-proteins [serum FLC was not in use then].

The mini-allo-BMT procedure was new in 2000 when I enrolled with great expectations that a “new cure” for MM would result from this experiment. The total number of MM patients enrolled in this trial was only 54 and 98% survived the treatment [the first 6 months]. I felt a certain mixture of pride and relief as the tests continued showing my status as CR with no MM progression. During the first year after the mini-allo-BMT I experienced considerable fatigue, but I was very appreciative of the “second chance” given to me, and I still am and therefore can enjoy every single day as a very special gift. For this reason my awareness and appreciation of family and friends, music and nature are enhanced in many ways. And for me this compensates for the difficulties encountered during and after the various treatments.

RELAPSE AFTER MINI-ALLO-BMT: I suspected MM relapse already in March 2003 and December 2003 due to increasing bone pain in both the right and left hip [the iliac wings] and my subjective observation of unusual urine frothing and recurring night-sweats. Both times were after 8 weeks delay of Aredia infusion due to increased serum creatinine. In each case the results from bone survey, MRI, blood tests, serum electrophoresis and 24-h urine BJ-protein tests were all “unremarkable”. Yet, because the bone-pain disappeared within 8 - 10 days after Aredia infusion the determination of probable relapse was not made at that time. In January and April 2004 we tested for serum FLC-kappa [NR 0.3 – 1.9 mg/dl] and found 5.4 mg/dl and 2.3 mg/dl, but because the test was unfamiliar to the oncologist and there was no patient baseline to compare with, we really had no clue.

Starting in February 2004 my throat began to feel “lumpy” and my voice increasingly turned gravelly over the next 4 month. My oncologist suggested I consult with an otolaryngologist, who in turn treated me for acid reflux until he suspected and checked a “lumpy growth” in the larynges. My MM relapse was diagnosed in late June 2004 based on MRI followed by biopsy of a “solitary extramedullary plasmacytoma” [2 x 3 cm] in the laryngeal region both above and below the true vowel cords. The myeloma plasma cells were found to stain positive for FLC-kappa. However, no other indication of myeloma activity could be found with bone survey, MRI, serum Ig-electrophoresis or 24-h urine test [and serum-FLC-kappa testing was delayed until August due to lack of focus].

PHASE III TREATMENT: The first line therapy for solitary extramedullary plasmacytomas is radiation, and I received 3600 cGr over 28 days at the laryngeal plasmacytoma. The radiation “burn” was uncomfortably hot and the internal swelling eventually made eating and talking difficult for several weeks. But within 3 weeks post radiation most of the swelling had subsided and my voice was 60% recovered, and a MRI-scan 6 weeks post radiation showed that the plasmacytoma was well on its way to disappear. FLC-kappa showed rapid weekly increases from the time radiation was finished [69 mg/dl increasing to 83, 109, 163 at peak] then declining to 17 and 10 mg/dl and holding fairly steady for several weeks [confirmed by kappa/lambda ratio].

At this point it had become clear to me that the conventional oncologist approach, in the absence of Ig-secretion that can be monitored, was to wait until MM progression would announce itself by bone pain, lytic bone lesions and urine Bence-Jones protein. In other words, until “real damage was done” that could justify renewed therapy. However, suspecting that the elevated LC-kappa could be due to more MM activity outside of the laryngeal area we did a PET-PC scan. The scan showed 11 biologically active sites indicating aggressive MM progression [even if some of the sites might be “false positive” results]. Based on this evidence taken together with the elevated LC-kappa, we now could reason that additional chemotherapy indeed was justified to prevent multi-site runaway MM progression. At this point several treatment options were discussed, i.e., Thalidomide, Dexamethasone or Velcade as separate applications to better evaluate efficacy. The recommendation was to start with Thal although the literature indicates that extramedullary plasmacytomas are refractory to Thal, so that a patient prone to this phenomenon probably should be extra cautious.

For me it was not entirely unexpected that a relapse could happen after four years in CR post auto-mini-allo-BMT; and I approached the new state of affairs with confidence knowing about the many new therapies discovered and tested during this time span. I became increasingly concerned, however, as weeks went by and I noticed what I thought was missed opportunities for anticipatory action by my oncology team and detected a lack of sense of urgency regarding treatment and monitoring of my MMLC-secretor case [with FLC and PET-CT scan]. Their paradigm seemed to me to be that something has to go seriously wrong [noticeable and serious pain and bone damage] before intervention and treatment is initiated. My view, developed from my many years of experience in the petrochemical industry, is in summary that you cannot allow events to reach the point of runaway reactions, fires and visible damage before taking corrective action. At this point my conclusion therefore is that there is a need for a paradigm shift whereby the oncologist becomes more anticipatory in treatment and monitoring, and each MM-patient must be his own project manager in close cooperation with his physician and oncologist.

PHASE IV TREATMENT: As the first treatment option we used Thalidomide starting out at 50-mg/d and Dexamethasone 40 mg/week in September 2004. However, Thal was discontinued after just 3 weeks due to the rapid onset within a few days of the all its known side effects. In my case these were severe and included PN starting at feet and hands, burning sensation on arms and legs, mental changes, constipation, and random “pinprick” nerve assaults. In addition a severe skin rash started on day 2 at the radiated area, then spread down the breast and eventually down over the stomach. We concluded that GVHD could be or could become a factor in the Thal-induced rash and therefore stopped Thal. Meanwhile the LC-kappa remained near constant at 5 – 10 times normal [allowing for test error and flu-vaccination] and strong urine frothing indicated high B-J-protein load escaping the kidney [but otherwise good kidney function based on normal serum creatinine level]. The recovery from the Thal-rash/GVHD took 4 weeks. During these weeks I started with one 4-day 40-mg/d Dex-cycle and afterwards was tapering down with Dexamethasone and Prednisone and each weekend I took an antibiotic [Bactrin] to prevent lung infection.

7/17/05: Once the side effects from the prior treatment had disappeared in late October 2004, I started on the first of four cycles of Velcade at 1.3 mg/m2, two injections per week for two weeks and 10 days pause. Other than the expected decrease in platelet count, the side effects were almost not noticeable during the first two cycles, but at cycle 3, peripheral neuropathy [PN] had advanced to just below the knee and with cycle 4 it reached midway up the calf. Other increasing side effects observed were psychological, decreased mental concentration, pronounced fatigue and constipation [which I have learnt to mitigate successfully with Metamucil]. We also observed that my serum free light chain [FLC] had returned to normal range by December and we therefore stopped Velcade after the fourth cycle at end January 2005 [the “normal” treatment regime suggested 6 cycles].

In February, to obtain a reliable double-check on the MM-progression, I had a PET-scan and we found that just 6 of the prior 11 MM-hot-spots were showing positive activity [ambiguous, because it could also indicate active healing of damaged tissue]. To identify the most pronounced “hot-spot” we made a BMG using CT-scan to position the needle at the right spot in the Iliac, however we were not successful in getting sufficient blood sample at that location to make a meaningful test for MM. Since the FLC remained normal with only insignificant variations for the next 6 months [remember, I’m an Ig-nonsecretor] no further treatment was started. We discussed if Aredia should be restarted [for bone strengthening or as MM-preventive] but decided against because I had a history of 5.5 years on bisphosphonates [mostly Aredia and 6 months on Zometa]. The data on necrosis of the jaw resulting from extended treatment with bisphosphonates had just been published and suggesting caution after several years of treatment. In any event, my situation in March-05 was declared to be “probable-CR” with no identified MM progression.

The recovery from severe PN during the 6 months from end January to mid July was “interesting” and tedious. As the nerves recovered I would get feedback in the form of needle-pricks, small and big, lasting from a tenth of a second to two seconds several times an hour all over the feet and legs. The feet and lower legs were burning and very tender to touch [shoes, socks, bed linen even] – and although massages and warm water would help for 30 minutes, mental concentration and sleep were impacted. However, as the weeks went by the PN retracted lower on the legs, exponentially it seemed so that I could feel the progress every week at first and later every several weeks. The intensity and frequency of the PN pain eventually faded away down to the foot soles [as of July 2005].

(To be continued)


Site © 2000-2015 Dean Gallea (in loving memory of June Brazil)

Site © 1996-1999 June Brazil - Webmaster:
(To email story contributor, see address at top of story)