Do you administer induction chemotherapy such as 7+3 for myeloid sarcoma in fit patients who can tolerate it? What is the best way to treat myeloid sarcoma?
Myeloid sarcoma has to be treated as AML. In patients who are fit enough, the cytosine - anthracycline 7+ 3 regimen is the remission induction chemotherapy of chioce.
I treat myeloid sarcoma with /+3, however I add local radiotherapy. It's very important also the cytogenetic chracterization of myeloid sarcoma. Treatment should be also guided by cytogenetics.
The most common cytogenetics associated with myeloid sarcoma is t(8,21) right?
Prof. Leone,
I wonder if you give radiation to every body and when you give it.
Dr. Devasia,
I think you are right and t(8;21) is the most common cytogenetic abnormality reported in patients with myeloid sarcoma.
Recently we have had a patient with histologically verified myelosarcoma infiltrating pleura and lungs, and there was found infiltration 10% with AML blasts NPM-1 positive in the bone marrow. The patient was treated with 7+3 induction followed by HIDAC+Mitox and proceeded to allogeneic stem cells transplantation in the 1.st CR because of high-risc pattern of the disease. No radiotherapy was given to the patient.
Radiation therapy is to be considered in patients with 100% solitary myelosarcoma, in patients with residual tumor mass after chemotherapy or transplantation, or in patients with solitary myelosarcoma relapse after chemotherapy or transplantation. The decision depends also on the age, comorbidities, localisation, distribution of the myelosarcoma.
The situation must be considered individualy.
Dr. Vokurka,
Thank you for your reply which is helpful. Your patient was positive for NPM-1; however, you took the patient to transplant. May I ask what the patient's high risk pattern was? Thanks.
In NPM-1 positive patient we do not perform aloBMT in 1st.CR if no risc factors (i.e. FLT3, no-CR after inducton) are present. We consider myelosarcoma as a high-risk factor and moreover the patient was not in CR after the 7+3 induction.
Dr. Vokurka,
Thank you for your reply. I agree with your management. That patient did need an allogeneic hematopoietic stem cell transplant.
Dear Dr. Mojtaba,
I strongly agree with Dr. Vokurka who explained brilliantly the issue. I can only add that precisely depending on some facts (as the posible effects of radiation therapy on tissues where myeloid sarcoma is located attending to the risk of second neoplasms) we decide wether to use chemo alone or chemo + radiation, but it would always be a high risk patient. We had good results with cases using chemo+radiotherapy + aloBMT even when masses were located in delicate places as the CNS. Good luck with your case.
Dr. Roman,
I have recently had a patient who had myeloid sarcoma of the right orbit; I treated her with 7+3 and when her counts recovered, we started her on radiation. She is still getting XRT and tolerating it quite well.
Dr. Mojtaba,
The 7+3 protocol is the gold standard treatment we first consider to use for patients with AML wether if they have a myeloid sarcoma or not. Of course we do so after assessing patient´s status performance to know if he/she can face such a tratement with an acceptable risk/benefits balance.
Dr. Roman,
Thank you for your reply. I wonder if you incorporate local radiation in your therapeutic intervention for such patients.
I'm a solid tumor oncologist, no experience in AML at all, but some modifications were proposed to the 7+3, and in this, patient's age and comorbidity matter:
*Jpn J Clin Oncol. 2013 Aug 15.
The Effect of Decreased-dose Idarubicin for Elderly Patients with AML
Kobayashi T, Ichikawa M, Nannya Y, Kurokawa M.
Department of Hematology and Oncology, Graduate School of Medicine, The
University of Tokyo, Tokyo, Japan.
We evaluated whether reduced-dose chemotherapy with 2 days of idarubicin (12
mg/m(2)) and 5 days of cytarabine (100 mg/m(2)) (2 + 5) is effective for patients
aged 65-74 by retrospectively comparing the results with those aged 55-64 treated with 3 + 7. In 1999-2009, we treated 20 patients aged 65-74 with 2 + 5, and 23 patients aged 55-64 with 3 + 7. The complete remission rates by the first
induction were 50.0 and 69.6% for older and younger groups (P = 0.203). Two-year overall survival rates were 55.9 and 32.3% for older and younger groups; 2-year rates of relapse-free survival for all these patients were 15.7 and 36.5%. The differences in overall and relapse-free survival were statistically insignificant
(P = 0.726 and 0.413, respectively). The treatment results of 2 + 5 for the older
group were not significantly worse compared with those of 3 + 7 for the younger.
Therefore, elderly patients who do not tolerate 3 + 7 should still benefit from 2
+ 5.
PMID: 23956441 [PubMed - as supplied by publisher]
*Oncogene. 2013 Sep 12;32(37):4331-42. doi: 10.1038/onc.2012.469. Epub 2012 Oct 22.
Azacytidine and Erlotinib exert synergistic effects against AML
Lainey E(1), Wolfromm A, Marie N, Enot D, Scoazec M, Bouteloup C, Leroy C, Micol JB, De Botton S, Galluzzi L, Fenaux P, Kroemer G.
Author information:
(1)1] INSERM, U848, Villejuif, France [2] Institut Gustave Roussy, Villejuif, France [3] Hôpital Robert Debré, AP-HP, Paris, France.
The term myelodysplastic syndrome (MDS) identifies a heterogeneous group of
clonal disorders originating from bone marrow stem cells that often progress to
acute myeloid leukemia (AML). The reference treatments for MDS include the DNA methyltransferase inhibitors azacytidine and decitabine. Recently, the epidermal growth factor receptor (EGFR) inhibitor erlotinib has been shown to exert antileukemic activity in vitro and in vivo, independent of the EGFR. Thanks to this feature, Erlotinib is currently being tested as an antileukemic drug in
clinical trials. Here, we report that Azacytidine and Erlotinib mediate
synergistic antineoplastic effects in several primary or secondary (post-MDS) AML cell lines. The combination of Azacytidine and Erlotinib blocked cell-cycle
progression and induced caspase-dependent apoptosis more consistently than either of the two agents alone. These effects were not a consequence of cellular
differentiation and could be discriminated from each other, as the former
depended on caspases whereas the latter did not. The synergy between azacitidine and erlotinib, which involved the proteasomal degradation of the anti-apoptotic Bcl-2 family members MCL-1 and BCL2L10 and the upregulation of their pro-apoptotic counterpart PUMA, was abolished when azacytidine was replaced by decitabine but persisted when erlotinib was substituted with gefitinib, another EGFR inhibitor. Of note, the intracellular accumulation of azacytidine was
exacerbated by both erlotinib and gefitinib, pointing to a pharmacokinetic
mechanism of synergy. In approximately half of the cases studied, marrow and
circulating blasts from MDS and AML patients, respectively, exhibited
hyperadditive cytotoxic responses to the combination of azacytidine and
erlotinib. These results strongly suggest that the combination of azacytidine and
erlotinib may exert clinically relevant antileukemic effects.
PMID: 23085751 [PubMed - indexed for MEDLINE]
*Blood. 2008 Aug 1;112(3):760-9. doi: 10.1182/blood-2008-02-142687. Epub 2008 May 23.
Cyproheptadine displays preclinical activity in Myeloma and Leukemia.
Mao X, Liang SB, Hurren R, Gronda M, Chow S, Xu GW, Wang X, Beheshti Zavareh R, Jamal N, Messner H, Hedley DW, Datti A, Wrana JL, Zhu Y, Shi CX, Lee K, Tiedemann R, Trudel S, Stewart AK, Schimmer AD.
Princess Margaret Hospital, Ontario Cancer Institute, Toronto, ON, Canada.
D-cyclins are regulators of cell division that act in a complex with cyclin-dependent kinases to commit cells to a program of DNA replication.
D-cyclins are overexpressed in many tumors, including multiple myeloma and
leukemia, and contribute to disease progression and chemoresistance. To better
understand the role and impact of D-cyclins in hematologic malignancies, we
conducted a high throughput screen for inhibitors of the cyclin D2 promoter and
identified the drug cyproheptadine. In myeloma and leukemia cells, Cyproheptadine decreased expression of cyclins D1, D2, and D3 and arrested these cells in the G(0)/G(1) phase. After D-cyclin suppression, cyproheptadine induced apoptosis in myeloma and leukemia cell lines and primary patient samples preferentially over normal hematopoietic cells. In mouse models of myeloma and leukemia, cyproheptadine inhibited tumor growth without significant toxicity.
Cyproheptadine-induced apoptosis was preceded by activation of the mitochondrial pathway of caspase activation and was independent of the drug's known activity as an H1 histamine and serotonin receptor antagonist. Thus, cyproheptadine represents a lead for a novel therapeutic agent for the treatment of malignancy. Because the drug is well tolerated and already approved in multiple countries for clinical use as an antihistamine and appetite stimulant, it could be moved directly into clinical trials for cancer.
PMID: 18502826
*Leuk Lymphoma. 2014 Apr 11. [Epub ahead of print]
Low-dose homoharringtonine and cytarabine in combination with granulocyte
colony-stimulating factor for elderly de novo acute myeloid leukemia patients.
Chen C, Xu W, Yang J.
Abstract The treatment of a young patient with acute myeloid leukemia (AML) has
improved dramatically during the past several decades. However, management for elderly patients with AML still remains a challenge. HCG (homoharringtonine and cytarabine in combination with granulocyte colony-stimulating factor) regimen has shown promise for elderly patients with AML transformed from myelodysplastic syndrome (MDS). To our knowledge, the clinical effect of HCG regimen for elderly de novo AML patients has not been well evaluated. A total of 56 elderly de novo AML patients aged 60-80 years were enrolled in this study. All patients were treated with HCG regimen. The overall response rate was 75% (60.7%% CR and 14.3% PR). 14 (25%) of the 56 patients showed no response (NR). A higher CR rate was observed in patients aged
The decision for treatment does not depend on the chronologic patient age but on the biological age. At this monet I have a lady aged 71 years who is getting ready for allogeneic tranplant after 2nd. remission of AML.
Radiation is another thing, there is no contraindication, but these are the ages with higher incidence of COPD and other pulmonary problems that are important risk factors for invasive fungal diseases...
Dr. Mojtaba,
We do use to combine RT with 7+3 regimen, always making a previous evaluation of the different elements that every particular patient has regarding mass size and location, kind of affected tissue, performance status, previous history of RT (previous cumullative dosage exposure) and such...it is sort of a tailored decision with every new patient. Anyway we use RT only on the affected area not TBR that is why complications are generally manageable.
Dr Graymer:
All those studies are indead treatment alternatives but for de novo AML "7+3" stills gold standard. Even when 2+5 has been used since many years as an alternative for those patients with a poorer performance status (not older, because a joung patient may have a performance status that makes 7+3 a not suitable option) some other study groups like HOVON/SAAK (if I remember well the name) have demostrated very good results treating elderly patients with good performance status and AML secundary to MDS (very poor prognosis group usually refractory to treatment and short OS) with intensified versions of 7+3 using high dose daunorubicin. Side effects where not greatter than expected but results where significantly better. This strategy has been extrapolated to younger patients in an aproach directed to avoid earlier relapses.
Yes, is it a relapse of AML, although extramedullary. In a patient with good PS it is the first choice. I am little skeptical about involved field RT, as AML is a systemic disease and if untreated, it will appear elsewhere.
Chloroma is a subtype of AML, so if you consider RT, any standard AML Chemo Therapy is not only advisable, but mandatory, I'm not aware if concomitantly with the RT, of in a sequential way; sometimes peripheral blood Leukemia takes a while being detected after the Chloroma appeared, but Chloroma is to be treated always with CT, with or without RT,
Dear Dr Mojtaba Akhtari,
I do suggest to give 3+7 and some doses of HDCA. Later, if bone marrow is not involved autologous stem cell transplantation can work in myeloid sarcoma.
Recently one of our paper entitled "Life and Consciousness - The Vedāntic View" has been published in the Journal Communicative & Integrative Biology. An interesting discussion on this paper can be found at: https://groups.google.com/forum/#!topic/online_sadhu_sanga/Mcv2O-yhqLE
From paper:
"The scientific confirmation of the existence of consciousness in unicellular organisms and plants certainly establishes that the brain is not the source of consciousness. Several decades back, research in medical science has also proven that the brain is not the source of consciousness. In 1970, Robert White and his team successfully transferred the head of a rhesus monkey to the headless body of another monkey. The monkey survived for 8 days.68 Researchers are also attempting to perform the same scenario with human beings.69 It is reported that if a human head has been detached under controlled conditions, it must be reconnected to the circulatory flow of other person's body (which is conscious or living) within one hour.70 Therefore, brain-based analysis for understanding consciousness (neuronal analysis) does not have very bright prospects."
Paper: Life and Consciousness - The Vedāntic View
DOI: http://dx.doi.org/10.1080/19420889.2015.1085138
Journal: Communicative & Integrative Biology
Publication date - 09 Oct 2015
Author: Bhakti Niskama Shanta - http://orcid.org/0000-0002-2039-3249
- Badges
- Science topic