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Weekend at Nexus

Lately, my weekends had been taken up by Pharmaceutical events. It appeared that they had been taking a hiatus during the Ramadan months, and now it was payback time. Added that to the wedding invitations and other commitments, my weekends seemed to be full lately.

Today, it at Bangsar South, at a venue called Nexus to be exact. To be honest, Anita was more familiar with the place, and it was only a five minutes drive from my apartment.

The event was an update to the European Haematology Association meeting - which I did not attend - back in June, covering a wide range of malignant haematology subjects. The Saturday program started from 8 am, which I had to miss due to my clinic. I joined the "party" after lunch, just in time to catch the afternoon case presentations. Tomorrow would be a half day do, followed by lunch. This was followed by the MSH Council meeting and early buffet dinner at the serviced apartment cum hotel next door - called Capri - where the outstation delegates stay.

I may have to start my ward round early since the topic looked rather interesting. Then it would be a quick outing with the boys since school term would start again next Tuesday. Another long day tomorrow.

A Day in Putrajaya

I spent the best part of the days today in Putrajaya being immersed into the new Dengue treatment guideline. Certainly there is a fight shift in the treatment algorhitm compared to the last guideline from 2009.

It creator looked neat on paper, easy to follow but my main worry was the input mainly came from the Government Doctors and I worry that they may not under stand limitation of these guideline in the private setting. The practice guideline which they talked about was more on the clinical part, and as a hospital maybe SJMC may need to modify some of the nursing pathways to accommodate. Patient placement in the ward is one of the issues, as the paying customers were more keen on the size of their rooms rather than the monitoring level which the nurses could provide.

The fluid resuscitation regime appeared more systematic, with emphasis on oral fluid intake. Criteria of admission may not apply to Subang as most of time patients were admitted on their request. I was about to ask about whether the Private hospital can be more selective on their admission but that was going to be thorny issue.

I was not able to attebd tomorrow's chapter I was afraid since I would be having clinic. The topic tomorrow appeared more ICU and inpatient orientated, which was more relevant to my practice. Clearly plenty to catch although my current practice did not differ much from the gist of the discussion. At least the need for platelet transfusion was laid out as I still think that there is too much pressure to transfuse either from lack of knowledge, fear if impending deterioration as well as pressure from patients and their relatives. I felt that we a plus have a poster at the Casualty spelling out that platelet transfusion does not cure dengue. The recent drama about papaya leaf also did not help matters.

On the whole, a fruitful day.

Transplant for the Elderly in Myeloma

They chose a dose of melphalan known to be tolerated in this age group and augmented its activity by using cassettes of treatment using novel agents during induction, consolidation, and maintenance and evaluated its activity and tolerability in the 65- to 75-year-old age group. It is clear that it is well tolerated, with minimal early mortality and is associated with good response and survival data. It is possible to compare these outcomes with representative historical data sets including the Medical Research Council (MRC) study where the overall survival (OS) in the nontransplanted group for melphalan-prednisone vs cyclophosphamide-thalidomide-dexamethasone was 30.6 vs 33.2 months, respectively, and for patients in the transplanted group >64 years of age was 53 months.2 In the Intergroup Français du Myélome (IFM) 99-06 study comparing melphalan-prednisone with melphalan-thalidomide-prednisone and with autologous stem cell transplant (ASCT) with 100 mg/m2 of melphalan, the OS in each group was 33.2, 51.6, and 38.3 months, respectively.3 Thus, the 5-year OS of 63% in the current study is good, using this novel sequential approach to treatment, which should now be evaluated formally against current standard approaches for this age group.

Maximizing cure rates by personalizing therapy is one of the major aims of modern myeloma treatment. With respect to achieving cure, one of the major prerequisites is the achievement of a stringent complete response (sCR) as assessed by multiparameter flow cytometry. It has been increasingly possible to achieve this aim in younger patients treated with ASCT where such sCRs are associated with optimum clinical outcomes.4 The integration of novel therapies into the context of ASCT has further improved overall and sCR rates and has changed the prevailing treatment paradigm which now comprises induction, transplant, consolidation, and maintenance treatment blocks. These blocks of treatment are delivered with the aim of sequentially reducing tumor bulk and incorporate the concept of using combinations of drugs incorporated into cassettes of treatment, which when combined have synergistic effects maximizing response rates. In addition, at each treatment phase, different cassettes comprising different combinations of drugs are given with the aim maximizing the chance of inducing apoptosis in resistant subclones and reducing the risk of relapse. More recently, the aim of maximizing responses has incorporated the concept of “maintenance treatment,” whereby ongoing treatment is given aiming to control the biology of residual clonal populations and killing myeloma stem cell populations coming into cell cycle.5,6

The incorporation of these ideas has revolutionized the treatment of younger patients, but it has come at the price of potentially increasing toxicity that needs to be managed. This is perhaps not an issue for the 40% of patients who develop myeloma before the age of 60, but for the majority of patients who develop myeloma beyond this age, toxicity is a significant issue. ASCT is considered the standard treatment of younger fitter patients, but there is no consensus in terms of an age cutoff above which ASCT is contraindicated. The initial IFM study used 60 years as an age cut point, whereas the MRC VII study used 65 years.7,8 In subsequent studies, including Myeloma IX, the MRC group used doctor and patient preference to decide on treatment pathway and included patients up to the age of 73 years in the transplant strategy. In an analysis of this study based on 5-year age cohorts, it was clear that there were differences in survival for the 55 to 60, 60 to 65, and 65 to 70 year groups, but mortality was not an issue. Interestingly, although a small number of patients over the age of 70 were included in the study, none made it to the transplant procedure for a number of reasons, including failure to collect stem cells and doctor or patient preference, making 70 a pragmatic age cutoff above which a full dose of 200 mg/m2 is generally inappropriate.2