Where to begin? Oceana growls as 4:30 in the afternoon passes and she still trying to sleep as the nurse comes in to check her vitals (every four hours). Sleep, sleep, sleep... okay, you know, it is a concept that is not half bad. After all, Oceana is free in her mind and is hopefully not dreaming about being bound to a "roller pole", confined to a bed. Do I have the heart to wake her up, well yes! She'll be up until 5 am at this rate and I need to be in the Hamptons by 10:30 am tomorrow! Sleep later, darling, get up for now!
I had written in the previous post that we were scheduled to do a BMA and LP on July 26th. Well, that didn't happen. After reviewing Oceana's previous phases, I discovered a pattern to her recovery. Essentially, she shows ANC at a low number and then the next day, reverts back to zero. During the last phase it took Oceana 8 days for her to establish an upward trend establishing count recovery. On July 25th, I convinced the Docs that we should wait as she had shown an ANC of 28 on July 21st and that according to my calculations would be producing neutraphils any day! Well, this time the resurgence of ANC did not occur until 11 days later. On the 11th day before we had the lab results, I had finally agreed to the BMA and LP as I began to get concerned and felt it was important to know how Oceana's marrow was faring. A very difficult decision to make as Oceana tormented me with "Why am I letting them do this" to her! The reason being that God forbid she was relapsing, how could I justify the delay in letting the Docs get a handle on it, if indeed this was the case. Considering how simple the procedure is, I did not want to be responsible for the guilt that would follow if her condition had worsened due to me delaying the impending treatment. Fortunately, after the results were analyzed, Oceana showed "0" leukemia cells in both her central nervous system and her bone marrow! What a relief.
When we returned to the room, we learned that she had shown an ANC of 20. Excellent! More good news. Finally, that evening when the Docs discussed the results, they suggested G-CSF. This would be administered as a daily shot. I immediately cringed. It was a week ago that I had spoken with two different Docs that had stated they would not be recommending this growth hormone for an AML patient. I couldn't believe what I was hearing! Are you kidding me? The Docs want to administer G-CSF to stimulate white blood cell count, thus enabling us to discharge sooner. However, we would have to come in to outpatient clinic regularly for hemogoblin and platelets as the growth hormone does not do anything for this. Essentially, the G-CSF would allow the hospital to release us earlier but at what risk? It is true that not only does the growth hormone promote white blood cells, but it could also promote myeloid cells. Since Oceana had been clear or myeloid cells before in her CNS (a known sanctuary for myeloid cells) followed by a relapse in her CNS, I am not willing to take the risk of assuming that there are not any myeloid cells left to stimulate!
We will wait for Oceana to recover on her own, thank you!
And as the choice was made Monday, Oceana showed an ANC of 40 on 8/5 and 60 and on 8/7. The upward trend has begun, despite the Docs prediction that her bone marrow was going to take a long while to recover. Oceana may still recover in time to make our family reunion on the 15th!
Below, I have included supporting evidence supporting the fact that G-CSF is not healthy for childhood AML.
Originally published as JCO Early Release 10.1200/JCO.2009.25.9010 on April 20 2010
© 2010 American Society of Clinical Oncology.
Granulocyte Colony-Stimulating Factor (G-CSF) Treatment of Childhood Acute Myeloid Leukemias That Overexpress the Differentiation-Defective G-CSF Receptor Isoform IV Is Associated With a Higher Incidence of Relapse
From the Department of Pediatric Hematology and Oncology and Institute of Cell and Molecular Pathology, Medical School Hannover, Hannover; Pediatric Hematology and Oncology, University of Frankfurt, Frankfurt; Justus-Liebig-University, Department of Pediatric Hematology and Oncology, Giessen; Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster, Germany; Department of Pediatric Hematology and Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands; University Hospital Motol and 2nd Medical School, Charles University, Prague, Czech Republic; and St Anna Kinderspital and Children's Cancer Research Institute, Vienna, Austria.
Corresponding author: Stephanie Ehlers, MD, Pediatric Hematology and Oncology, Medical School Hannover, Carl-Neuberg-Str 1, D-30625 Hannover, Germany; e-mail: ehlers.stephanie@mh-hannover.de.
Purpose This prospective, multicenter Acute Myeloid Leukemia Berlin-Frankfurt-Muenster (AML-BFM) 98 study randomly tested the ability of granulocyte colony-stimulating factor (G-CSF) to reduce infectious complications and to improve outcomes in children and adolescents with acute myeloid leukemia (AML). However, a trend toward an increased incidence of relapses in the standard-risk (SR) group after G-CSF treatment was observed.
Patients and Methods Of 154 SR patients in the AML-BFM 98 cohort, 50 patients were tested for G-CSF receptor (G-CSFR) RNA isoform I and IV expression, G-CSFR cell surface expression, and acquired mutations in the G-CSFR gene.
Results In patients randomly assigned to receive G-CSF after induction, 16 patients overexpressing the G-CSFR isoform IV showed an increased 5-year cumulative incidence of relapse (50% ± 13%) compared with 14 patients with low-level isoform IV expression (14% ± 10%; log-rank P = .04). The level of G-CSFR isoform IV had no significant effect in patients not receiving G-CSF (P = .19). Multivariate analyses of the G-CSF–treated subgroup, including the parameters G-CSFR isoform IV overexpression, sex, and favorable cytogenetics as covariables, revealed the prognostic relevance of G-CSFR isoform IV overexpression for 5-year event-free survival (P = .031) and the 5-year cumulative incidence of relapse (P = .049).
Conclusion Our results demonstrate that children and adolescents with AMLs that overexpress the differentiation-defective G-CSFR isoform IV respond to G-CSF administration after induction, but with a significantly higher incidence of relapseFrom the Leukemia Research
"In recent years, many cytokines have been defined and some of them used clinically. In hematological malignancies, cytokines, including granulocyte colony-stimulating factor (G-CSF), have been widely used for leukopenia after chemotherapy. However, in acute myelogenous leukemia (AML), some leukemic cells may be induced to proliferate by these cytokines and they must be used with care. In this study, we have investigated cell reactivity and proliferation with G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CMF), macrophage colony-stimulating factor (M-CSF), stem cell factor (SCF) and thrombopoietin (TPO) in cases of AML. We have also investigated the reactivity of some myeloid leukemia cell lines to TPO. G-CSF, GM-CSF, M-CSF, SCF and TPO caused proliferation of leukemic cells in 25%, 58.3%, 8.3%, 21.1% and O% of cases, respectively.
Because of this result, the use of G-CSF in AML should be regarded as potentially hazardous."
Leukemia Research
Volume 22, Issue 6, June 1998, Pages 557-560
Hi,
ReplyDeleteJust read through your blog... Jamie had forwarded it on to read. My son, Ben, was in CHOP last year for AML for over 7 months.... so I can relate to how you are feeling right now. The last round is the worst.... exhaustion, both physical and mental.... broken down wondering how you are going to make it one more day... the longest round with counts taking forever to recover, wondering if you will ever get a full night's rest again without a monitor going off andd feeling like you can't make it one more day in a hospital. I just wanted to say HANG IN THERE... YOU ARE ALMOST THERE! IT'S the final stretch and it sucks... but know that you have it in you to make it through.
Just wanted to send you a bit of support.
Best.
Elise Whitaker
Right on, Dave! Hang tough!
ReplyDeleteLove, Nick