More CMML links

These are studies and summaries of studies from some official sources, describing the disease in more detail, and also giving some sort of overview of the treatment.

Treatment Overview for Myelodysplastic/ Myeloproliferative Neoplasms (among which CMML is the primary disease in the category). Scroll down:

In a recent review of 50 allogeneic transplantations for CMML (i.e., median age 44, age range 19–61 years) from related (n = 43) or unrelated (n = 7) donors, the 5-year-estimated overall survival was 21%. The 5-year estimated probability of relapse was 49%. The data showed a trend for a lower relapse probability of acute graft versus host disease grade II through grade IV and for a higher relapse rate in patients with T cell-depleted grafts, suggesting a graft-versus-CMML effect. This latter series represents the largest cohort of patients with adult CMML and allogeneic stem cell transplantation to date.

Risk assessment in chronic myelomonocytic leukemia (CMML):

The clinical course of chronic myelomonocytic leukemia (CMML) is extremely variable, and disease progression can occur at any time from diagnosis. Median survival is about 20 months. About 20% of patients develop acute myeloid leukaemia (AML). Multivariate analyses performed by several groups showed that elevated medullary blast count, low haemoglobin, elevated serum lactate dehydrogenase (LDH), and perhaps an increased lymphocyte count, are the most important independent prognostic parameters

Outcomes in lower-risk MDS and CMML

CMML is an uncommon clonal disorder of the bone marrow that has been classified as a myelodysplastic/myeloproliferative (MDS/MPS) according to WHO classification given its heterogeneous clinical, hematological and morphologic features.2 The median survival in CMML is 18 to 20 months from diagnosis. Subset analysis on patients diagnosed with CMML from existing decitabine [similar to Vidaza] trials has offered invaluable insight on the management of a disease that is difficult to treat as there are few studies to date that study CMML alone. The experience with decitabine in CMML was demonstrated in three open-label and single-arm multicenter Phase II studies and a multicenter Phase III study retrospectively reviewed by Wijermans et al. Overall, results from those 4 studies demonstrated an ORR of 26% (10% CR + 16% PR), a HI of 19%, a median of 15-month survival from initial decitabine treatment (95% CI, 8 to 22 months), and a 2-year survival of 25%. In the trial conducted by Aribi et al to evaluate the activity of decitabine in patients diagnosed with CMML, 19 patients with CMML were given 1 of 3 schedules of decitabine with total dose per course of 100 mg/m2.34 The study design dictated repeated courses every 4 weeks for a minimum of 3 courses without dose escalations. Results demonstrated an ORR of 68%, a CR of 58%, a HI of 11%, and a 2-year survival rate of 48%. Patients were exposed to a median of 9 courses of decitabine. Larger randomized trials featuring patients with CMML are needed to further establish the potential of decitabine for this difficult to treat disease.

ORR = overall response rate
CR = complete remission
PR = partial remission
HI = hematological improvement

This article seems to represent the response rates from treatment of “lower risk” patients, maybe older patients, who won’t receive a transplant.

Conscious sedation and “the disease process”

It was a day of mixed emotions at the hospital yesterday. Beth said that the bone marrow biopsy was “the best ever” – essentially pain-free and she doesn’t remember a thing. The “conscious sedation” apparently knocked her out instantly.

On the down side, Beth’s hemoglobin numbers continue to fall – she fell below the magical 8.5 level, and she needed to get a couple more blood transfusions. If you’ve been reading at all, you know we’ve been keeping a pretty close watch on the “blood charts”, and there was a new number yesterday: LDH.

LDH stands for lactate dehydrogenase and the LDH test [oddly enough] measures the amount of LDH in the blood. Beth’s number was 621, and the normal range indicated on the lab test was 100-216. We didn’t recall seeing that number before, and quite naturally, we were alarmed.

“What does that mean?” we asked the nurse.

Immediately she said, “that’s the disease process”. And she frequently works with transplant patients, and so she knows what she’s talking about.

According to the NIH link, above, it could indicate many things, including “new abnormal tissue formation (usually cancer)” or “tissue death”. None of the things it indicates seems to be good.

She had been kind enough to get this chart for her in the first place (I ask everyone I can about getting these charts), and she was also kind enough to get us some additional information on it. We emailed Dr. Rossetti, and he said, “The LDH is somewhat non-specific. It could mean recovery after the last cycle or could suggest disease. The [information from the bone] marrow [biopsy today] will indeed give us the answer.” So we will know something more definite when we get the results from the biopsy.

Comparing LDH readings, June and September

Now, when we got home, we went back and looked at some past blood charts, and that number had been measured, during her first stay at West Penn, back in June. The number at the time was 549. So, given that she has leukemia, it doesn’t seem out of the ordinary that this number would be so high. What is still a bit distressing is that it seems to be going the wrong way.

But we should know more about it in a few days.