Treatment for Chronic Lymphocytic Leukemia

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Question:

There’s been a lot of research, particularly at Memorial Sloane Kettering Cancer Center regarding circadian administration of chemo. However, I’m not aware of any published data specific for CLL. Do you have any references?

For which diseases this has been studied, Paul? My daughter always had her chemos in the early afternoon (after the results from the blood tests done in the morning were known). She had MOPP/ABV for advanced HD, with excellent results (CR after 6 cycles). Regards, Rob. PS Taking into account the circadian rhythms of the medical staff, I would suppose that at night they would be more error-prone than they are at daytime. Rob.

Response:

(snip) Using MedPublish (at http://www.ncbi.nlm.nih.gov/PubMed/medline.html) to search the medical literature (and using advanced searching so I could do a boolean search for articals discussing circadian and cancer and drug (or chemo) therapy found 276 references. Feel free to perform this search and download any references of interest.

Response:

Using MedPublish (at http://www.ncbi.nlm.nih.gov/PubMed/medline.html) to search the medical literature (and using advanced searching so I could do a boolean search for articals discussing circadian and cancer and drug (or chemo) therapy found 276 references. Feel free to perform this search and download any references of interest.

Thanks, I’ll have a look. Rob.

Response:

(snip) There’s been a lot of research, particularly at Memorial Sloane Kettering Cancer Center regarding circadian administration of chemo. However, I’m not aware of any published data specific for CLL. Do you have any references? DISCLAIMER: Please note that all contents of this message, including any advice, suggestions, and/or recommendations has NOT been generated as part of any professional evaluation. No patient has been examined prior to making these comments; no professional fee has been charged by or paid to myself. The reader is advised to discuss these comments with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that in answering an electronicly posted question, I am NOT creating a physician — patient relationship. As I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur. Finally, the material produced by myself may be reproduced for personal use, provided that appropriate credit is given; but this material may not be reprinted or reproduced in any format for any other purpose.

Response:

Dear Prasana: I am not a doctor and can’t comment specifically on these medicines. I would observe, though, if it can be of any use, that any chemotherapy (fludarebene, e.g.) must be done AT NIGHT. Chemotherapy done at night will be most likely to decrease the number of CLL cells and the fewest number of healthy platelets and other blood cells, and leave room in the marrow and blood stream for more healthy blood cells to multiply – which I guess would be the real solution for the problem of spontaneous bleeding. Chemotherapy done in the MORNING, on the other hand, is BAD, because it would kill the FEWEST number of CLL cells and, given the results of studies on circadian rhythms and also my father’s experience in his first 2 cycles of chemo, the LARGEST number of healthy blood cells including platelets, thus endangering the life of the patient. (I really can’t emphasize this enough.) Your friend’s father’s situation sounds serious. I will tell you that my father had 4th-stage CLL with a very low platelet count 2 years ago, including internal bruising and spontaneous hairline cuts which got infected (my father’s neutrophil counts were also quite low, and he also had low RBC counts, resulting in anemia). My father had fludarabene chemotherapy at night, around 10:30 P.M., with neutrophil colony stimulating hormone (?) given at twice the usual dose after the week of chemotherapy in most of the cycles. He is now in full remission, and highly functional. I really don’t know if any of this is of help. My sympathy and best wishes! Sincerely, Michael

Response:

(snip) The management of thrombocytopenia in CLL can be difficult when the mechanism appears to be increased platelet destruction, rather than the (much) more common mechanism of marrow replacement as commonly seen in advanced CLL. In this case I would wonder about the following: 1. Is there significant splenomegally? If so (and the marrow clearly shows increased thrombopoiesis) then perhaps splenectomy would be of value. 2. Has a drug designed to block splenic sequestration (immunoglobulin, danacrine) been tried?? 3. Fludarabine rather than chlorambucil is now the drug of choice for CLL. However, coadministration of fludarabine and steroids carries a very high risk of infection due to immune suppression. When my partner’s niece had ALL, he was pleasantly suprised to find the gov’t supported medical school hospital in New Dehli was run by a former National Cancer Institute Fellow and that treatment approaches in India were similar to those that we are using in the U.S. DISCLAIMER: Please note that all contents of this message, including any advice, suggestions, and/or recommendations has NOT been generated as part of any professional evaluation. No patient has been examined prior to making these comments; no professional fee has been charged by or paid to myself. The reader is advised to discuss these comments with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that in answering an electronicly posted question, I am NOT creating a physician — patient relationship. As I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur. Finally, the material produced by myself may be reproduced for personal use, provided that appropriate credit is given; but this material may not be reprinted or reproduced in any format for any other purpose.

Response:

My good friend’s Father has been recently diagnosed with Chronic Lymphocytic Leukemia. I am attaching his request for posting the case summary and would request anyone with information of possible options to please respond to us. The family is very concerned and is looking for any possibilities for a treatment. Thank you, -prasana I am enclosing dad’s case study document in word format, html and text format. Can you please post it on some of the sites at stanford, and other web sites which may be able to help us in identifying the cause of the problem. The doctors here have concluded that he has CLL (Chronic LymphocyticLeukemia) and they think that this is what is causing the distruction of the platelets. We have started the treatment for CLL hoping that it will stop the platelet distruction. So far we have not seen any positive results from this current medacitions. We just want to confirm if the course of actions being taken at our end are correct. Let me know if u need any more info, also can u please include my e-mail address in the posting. Rajan Lohar

[ CASE SUMMARY.html 21K ]

DATE

TLC

PLATELETS

28.11.97

13.6

14600

2000

30.11.97

14.3

27500

4000

01.12.97

13.7

32500

2000

IVIG

02.12.97

13.2

34500

3000

IVIG

03.12.97

13.6

40200

21000

04.12.97

14.2

49700

5000

05.12.97

14.6

47400

1000

06.12.97

13.7

48000

2000

07.12.97

14.3

52700

1000

CASE SUMMARY.doc

< 1K Download [ CASE SUMMARY.txt 3K ]

CASE SUMMARY 12.12.97 Patients Name .. Mr. P. D. Lohar Age.. 70 yrs Male. K/C/O Arthritis X 30 yrs. Initially treated as RA. Received Zyloric , Colchicine. Colchicine stopped one and a half year back. Now on T.Zyloric 100 mg . 1 BD. T Darvocet Zyloric stopped , Darvocet stopped — 30.11.97. C/o Bleeding from gums started on 23/11/97. 25/11/97 Platelets 10,000 Bone Marrow revealed normal picture. S/o ITP Received 5 pints daily x 3 days. No H/o Melena, Haemoptysis, personal H/o No addiction. No Diabetes. Reflexes normal. BP normal. No fever or any other symptom. Sonography results show that Spleen , Gall bladder, Liver are normal. No excess fluid seen. Vitals (N), Purpuric spots all over body. No LN Pathy No clubbing. RS, CVS, PA – NAD DATE HB TLC N L E M PLATELETS 28.11.97 13.6 14600 62 29 3 – 2000 30.11.97 14.3 27500 71 26 - 03 4000 01.12.97 13.7 32500 72 24 - 04 2000 IVIG 02.12.97 13.2 34500 64 26 - 10 3000 IVIG 03.12.97 13.6 40200 45 49 - 06 21000 04.12.97 14.2 49700 44 50 - 04 5000 05.12.97 14.6 47400 54 33 - 13 1000 06.12.97 13.7 48000 37 52 - 06 2000 07.12.97 14.3 52700 27 69 - 04 1000 08.12.97 14.4 59600 1000 09.12.97 13.9 56200 39 58 - 3 1000 10.12.97 13.2 61000 45 64 - 07 5000 11.12.97 13.8 64200 38 51 4000 12.12.97 12.6 55500 43 55 - 02 2000 13.12.97 11.8 54700 47 51 4000 14.12.97 10.5 57300 46 46 1000 15.12.97 9.0 47500 47 44 8000 16.12.97 8.1 42000 47 52 2000 17.12.97 7.6 40100 55 37 1000 2 pints blood 18.12.97 11.1 30500 1000 Treatment Given T. Prednicolone 60mg / tds (Started on 28/11/97) T. Prednicolone 40mg / tds (Reduced as of 08/12/97) Inj. (IVIG) Immunoglobulin Human 1gm / kg / day x 2 days Wt. 53 kg (given on 1st & 2nd Dec 1997) DIC Profile PTT 21.6 / 21.0 PT 10.5 / 10.8 Fibinogen split produce 5 to 20 Fibrinogen 160 ( 150 – 450) XRC WNL Urine ( R ) WNL ANA -ve HIV -ve ECG – Chronic Atrial Fibrillation ESR 15 USG Abd – No splenomegaly Report of Bone-marrow Aspiration prepared on 10/12/97 Cellularity : Normocelluar. M : E Ratio : 9 : 1 Erythropoiesis : Relatively Suppressed; normoblastic. Myelopoiesis : Normal Maturation and distribution of granulocytic precursors. Lymphopoiesis : lymphocytes are increased ( 33% ) : Blasts – occasional Megakaryopoiesis : Megakaryocytes are increased in number. Impression : There is an excess of lymphocytes in the bone marrow. : Thrombocytopenia is of peripheral origin . Report of Bone-marrow trephine biopsy (10.12.97) Sections of bone-marrow trephine biopsy show an excess of mature lymphocytes which is both diffused and patchy in distribution. Erythropoiesis, granulopoiesis, and megakaryopoiesis are well represented. In view of peripheral blood lymphocytosis this could suggest a lymphoproliferative disorder. Example, Chronic Lymphocytic Leukemia. Please co-relate with Immunophenotyping findings. Cell Surface Markers Test (i.e. Immunophenotyping) (13.12.97) Findings suggests CLL ( Chronic Lymphocytic Leukemia) Dr. A. Das Gupta Consultant Haematologist. Present Treatment Leukeran 5 mg 1 – 1 for 4 days (started on 15.12.97) T. Donstal T. Zyloric 100 mg 1 – 1 – 1 T. Sepmac 1 – 1 Isomex Dulcolax T. Prednicolone 15 mg Wincrystine 2 mg ( given on 17.12.97) The patient is still bleeding from the gums and has developed blue-black patches all over the body, the biggest on the lower back ( 3

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