Cancer Treatment

Hyperfractionated radiotherapy in head and neck cancer

Hyperfrationated radiotherapy has been extensively studied, both in the treatment of head and neck cancer and in other cancer types. Hyperfractionated radiotherapy (multiple fractions per day) yields higher rates of acute toxicity compared with conventional radiotherapy (one fraction per day, five days per week). Data on the incidence and severity of late complications associated with hyperfractionation are incomplete. It is premature to conclude that hyperfractionation with dose escalation does not increase late tissue complications.
Although the improvements in loco-regional control and survival are promising, longer follow-up and more complete information on late complications will be needed to meaningfully compare these results to those achieved with concomitant chemoradiation in locally advanced squamous cell carcinoma of the head and neck.
A recent guideline concluded that conclusions regarding loco-regional control are limited by the quality of the published data. To date, only three of seven randomized controlled trials have provided convincing evidence of improved loco-regional control with hyperfractionation compared with conventional radiotherapy. In one of these three studies, improved loco-regional control was accompanied by an increase in overall survival. Two other randomized controlled trials have documented improved overall survival with hyperfractionation, but both studies have been criticized for failing to report complete data. Another emtaanalysis, hosever, concluded that altered fractionated radiotherapy improves survival in patients with head and neck squamous cell carcinoma and that comparison of the different types of altered radiotherapy suggests that hyperfractionation has the greatest benefit. The issue requires more study and the propsoed treatment should be considered experimental.

Head and Neck Cancer Disease Site Group. Mackenzie RG, Hodson DI, Browman GP, Zuraw L. Hyperfractionated radiotherapy for locally advanced squamous cell carcinoma of the head and neck [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2003 Jan [online update]. 13 p. (Practice guideline report; no. 5-6b). [22 references]

Lancet. 2006 Sep 2;368(9538):843-54. Links

Overgaard J, Audry H, Ang KK, Saunders M, Bernier J, Horiot JC, Le Maître A, Pajak TF, Poulsen MG, O'Sullivan B, Dobrowsky W, Hliniak A, Skladowski K, Hay JH, Pinto LH, Fallai C, Fu KK, Sylvester R, Pignon JP;Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis.Bourhis J,  Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH) Collaborative Group.Comment in:
Lancet. 2006 Nov 25;368(9550):1867-8; author reply 1868.
Lancet. 2006 Nov 25;368(9550):1867; author reply 1868.
Lancet. 2006 Sep 2;368(9538):819-21.
Republished in:
Clin Otolaryngol. 2007 Apr;32(2):119.

nccn.org, head and neck cancer

Donor lymphocyte infusion to treat chimerism

The donor cell reinfusion in this case is not being used to provide new graft versus leukemia effect but to destroy remaining normal patient cells and to provide engraftment. It ahs been observed that chimerism is risk factor for relapse of the leukemia. The status of DLI to treat disase is still unsettled and the use of DLI to decrease chimerism is even less established. There would have been no objection to a reinfusion of stem cells to re-engraft which I would see as a continuation of the previously approved stem cell transplant. However, using DLI in this fashion is experimental since the contention that it does os is supported by case reports and series only

Because of the large number of acute leukemia patients who relapse after alloBMT, there has been a substantial experience in the treatment of these patients with DLI. Using median doses of >/=108 T cells/kg, DLI alone induces complete remissions in 8% of patients with ALL and 22% of patients with acute myeloid leukemia (AML). When patients who receive chemotherapy prior to DLI are included, complete response rates are significantly higher, ranging from 33% to 37%. However, follow- up of ALL patients reveals few, if any, long-term survivors, although 1 has been reported. Relapse occurs in approximately one quarter to one half of patients with AML in remission after DLI, leaving a long-term survival rate of approximately 10% to 15%.

DLI has been researched as a treatment for a variety of hematologic malignancies, including most prominently chronic myeloid leukemia, but also acute myeloid leukemia, acute lymphocytic leukemia, multiple myeloma, myelodysplastic syndromes, chronic lymphocytic leukemia, Hodgkin’s disease, and non-Hodgkin’s lymphoma. Studies are limited due to small numbers but they have provided evidence that DLI can establish a graft-versus-leukemia/lymphoma effect.

Fewer patients with relapsed myelodysplasia have been treated with DLI. However, because myelodysplasia progresses more slowly than AML, the rate of complete remissions may be higher. The natural history of myelodysplasia patients who enter into a remission following DLI has not been described.

It is not clear whether administration of induction chemotherapy at the time of relapse improves long-term survival following DLI. It is usually thought that it does but without a strong conifrmation in the literature. A randomized trial with analysis performed on an intent-to-treat basis is needed to answer this question.

Litzow, Mark R Progress and strategies for patients with relapsed and refractory acute myeloid leukemia. Current Opinion in Hematology. 14(2):130-137, March 2007.

Luznik L, Fuchs EJ. Donor lymphocyte infusions to treat hematologic malignancies in relapse after allogeneic blood or marrow transplantation.Cancer Control. 2002 Mar-Apr;9(2):123-37.

Ishikawa J, Maeda T, Kashiwagi H, et al. Successful second allogeneic peripheral blood stem cell transplantation and donor leukocyte infusion in patients with relapsed acute leukemia using the same donor as for the initial allogeneic bone marrow transplantation. Bone Marrow Transplantation. 2003; 31:1057-1059.

Levine JE, Braun T, Penza SL, et al. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem cell transplantation. J Clin Oncol. 2002; 20(2):405-412.

E . Orsini , E . Alyea , A . Chillemi , R . Schlossman , S . McLaughlin , C . Canning , R . Soiffer , K . Anderson , J . Ritz Conversion to full donor chimerism following donor lymphocyte infusion is associated with disease response in patients with multiple myeloma . 
Biology of Blood and Marrow Transplantation , Volume 6 , Issue 4 , Pages 375 - 386, 2000

Suradej Hongeng et al, Donor Lymphocyte Infusion Can Eliminate Mixed Chimerism in Nonmyeloablative Stem Cell Transplantation for Correction of Hyper-IgM Syndrome Acta Hematologica Vol. 114, No. 3, 2005

Adjuvant chemotherapy and radiation for ampullary cancer

Carcinoma of the ampulla of Vater is defined as a malignant tumor arising in the last centimeter of the common bile duct where it passes through the wall of the duodenum and ampullary papilla. The pancreatic duct (of Wirsung) and common bile duct merge and exit by way of the ampulla into the duodenum. The ductal epithelium in these areas is columnar and resembles that of the lower common bile duct. Adenocarcinoma of the ampulla of Vater is a relatively uncommon tumor that accounts for approximately 0.2% of gastrointestinal tract malignancies and approximately 7% of all periampullary carcinomas.When possible, resection is the best treatment. Because local and systemic failures remain problematic, physicians continue to be interested in offering adjuvant therapy. The relative rarity of this disease limits research in this area.

There are many small studies and retrospective reviews that suggest that adjuvant chemoradiation may improve suvival. It is not likely that prospective comparative studies will be performed in this rare disease. A 2008 guidelines says: "As postoperative adjuvant chemotherapy, no effective adjuvant therapy has been established at the present time. It is recommended that further clinical trials, especially large multi-institutional RCTs (phase III studies) using novel agents such as gemcitabine should be performed as soon as possible in order to establish a standard treatment."

Furuse J, Takada T, Miyazaki M, Miyakawa S, Tsukada K, Nagino M, Kondo S, Saito H, Tsuyuguchi T, Hirata K, Kimura F, Yoshitomi H, Nozawa S, Yoshida M, Wada K, Amano H, Miura F
Guidelines for chemotherapy of biliary tract and ampullary carcinomas. J Hepatobiliary Pancreat Surg. 2008;15(1):55-62

S . Bhatia , R . Miller , M . Haddock , J . Donohue , S . Krishnan Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience . 
International Journal of Radiation OncologyBiologyPhysics , Volume 66 , Issue 2 , Pages 514 - 519

Autoimmune hemolytic anemia basics

Lay Summary: I discuss some very basic facts about AIHA.

Autoimmune hemolytic anemia (AIHA) due to the presence of warm agglutinins is almost always due to IgG antibodies that react with protein antigens on the red blood cell (RBC) surface at body temperature. For this reason, they are called "warm agglutinins" even though they seldom directly agglutinate the RBCs. IV Gammaglobulin blocks this process.

I some cases, AIHA can be characterised by a chronic course and an unsatisfactory control of haemolysis, thus requiring prolonged immunosuppressive therapy. Sometimes when medical measures fail, it may be necessary to surgically remove the spleen (splenectomy). The clinical course of the disease may show either resistance to steroids or dependence on high-dose steroids with subsequent development of severe side effects on growth, bone mineralisation, and the endocrine system. Splenectomy is effective in about 50 to 60 percent of the time in IgG antibody diseases but is not usually effective in IgM antibody haemolysis. Splenectomy is of benefit in these people because the spleen behaves like a sieve and if it is removed, even though the RBCs are coated by antibodies, they are no longer caught and destroyed in the spleen.

IVIG is an accepted treatment for autoimmune hemolytic anemia. Unlike steroids, it does not induce remissions but is a temporizing measure until a definitve treatment can be planned and delivered.  IVIG is not as effective in AIHA as it is in ITP. Other treatments can sometimes be used.

Ucar K. Clinical presentation and management of hemolytic anemias. Oncology [Huntingt] 2002;16(9 suppl 10):163-70.

Schwartz RS, Berkman EM, Silberstein LE. Autoimmune hemolytic anemias. In: Hoffman R, Benz EJ Jr, Shattil SJ, Furie B, Cohen HJ, Silberstein LE, et al., eds. Hematology: basic principles and practice. 3d ed. Philadelphia: Churchill Livingstone, 2000:624.

Hormonal adjuvant therapy including Lupron

In premenopausal women with early stage (stage I and II) breast cancer, the standard adjuvant treatment remains tamoxifen. Outside of a clinical trial, some doctors will add ovarian suppression to tamoxifen, and there is some evidence to support this approach. The evidence to support ovarian suppression is strongest in women who have not also received chemotherapy.

Outside of a clinical trial, I would generally recommend against an aromatase inhibitor with ovarian suppression in the vast majority of premenopausal women with early stage breast cancer who are starting on hormonal therapy. There are two international clinical trials that are comparing ovarian suppression plus an aromatase inhibitor with ovarian suppression plus tamoxifen or tamoxifen alone. These randomized phase III trial study ovarian suppression with either tamoxifen or exemestane to see how well they work compared to tamoxifen alone in treating premenopausal women who have undergone surgery for hormone-responsive breast cancer.

Use of ovarian supression with Lupron alone (without tamoxifen) is in trials it should be considered investigational.

In the Adjuvant Breast Cancer Ovarian Ablation or Suppression Trial, 2,144 premenopausal and perimenopausal women were randomized to tamoxifen alone or with the addition of ovarian ablation or suppression. They could also be given elective chemotherapy at their physician's discretion.
The hormone agonists used were 3.6 mg of goserelin (Zoladex) and 3.75 mg of leuprorelin acetate (Lupron). After an average 5.9 years of follow-up, the findings were (tamoxifen with ovarian ablation or suppression versus tamoxifen without ovarian ablation or suppression):

Those who had ovarian ablation or suppression were no less likely to relapse than those who did not (hazard ratio 0.95, 95% confidence interval 0.81 to 1.12, P=0.56).
Five-year relapse-free survival was similar between groups (73.7% versus 72.8%, absolute difference 0.9%, 95% CI -3.1% to 4.9%).
All-cause mortality was likewise similar between groups (HR 0.94, 95% CI 0.78 to 1.13, P=0.44).
Five-year survival was similar as well (82.6% versus 80.3%, absolute difference of 2.3%, 95% CI -1.2% to 5.9%). The findings were unchanged by adjusting for prognostic factors, including age, nodal status, and estrogen receptor status, or use of chemotherapy (overall survival P=0.50, relapse-free survival P=0.56).

As expected, ovarian ablation or suppression was more effective for the 39% of women whose tumors were retrospectively determined to be ER-positive. But even this group ovarian ablation or suppression did not have a significant benefit (HR 0.84, 95% CI 0.59 to 1.20).

There was a signal for benefit, though, in the small group of 56 women younger than 40 who did not receive chemotherapy. This "group considered biologically to have the most to gain from ovarian ablation or suppression" had a 0.55 hazard ratio for overall survival (95% CI 0.17 to 1.85).
The overall findings fit relatively well with those of the large meta-analyses of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG). As reported in The Lancet in 2005, ovarian ablation or suppression showed only a 3% absolute benefit for mortality after 15 years, though this was statistically significant (P=0.004).

In the second trial , the Adjuvant Breast Cancer Chemotherapy Trial, 1,991 women ages 26 to 81 were randomized to tamoxifen alone or with chemotherapy.  Adjusting for ovarian suppression use had little effect on the Adjuvant Breast Cancer Chemotherapy Trial findings.  Again, however, there was a suggestion that ovarian suppression may not be best in the setting of chemotherapy for premenopausal women.

In conclusion, despite some suggestion that a younger subgroup might benefit form ovarian ablation after chemotherapy, there was no solid proof. Ovarian ablation accompanied by tamoxifen is not proven by credible medical evidence to be beneficial for perimenopausal women. Lupron alone is certainly investigational and not medically necessary. This is especially so in an older woman who had also received chemotherapy.

Jonat W, Kaufmann M, Sauerbrei W, Blamey R, Cuzick J, Namer M, Fogelman I, de Haes JC, de Matteis A, Stewart A, Eiermann W, Szakolczai I, Palmer M, Schumacher M, Geberth M & Lisboa B 2002 Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with nodepositive breast cancer: The Zoladex Early Breast Cancer Research Association Study. Journal of Clinical Oncology 20 4628–4635.

Kaufmann M, Jonat W, Blamey R, Cuzick J, Namer M, Fogelman I, de Haes JC, Schumacher M & Sauerbrei W 2003 Survival analyses from the ZEBRA study. Goserelin (Zoladex) versus CMF in premenopausal women with node-positive breast cancer. European Journal of Cancer 39 1711–1717.

 Kellie L Jones and Aman U Buzdar A review of adjuvant hormonal therapy in breast cancer Endocrine-Related Cancer 11 (3) 391-406 

Compute Aided Detection (CAD) for MRI

Lay Summary: CAD is still investigational for breast MRI.

The use of computer-aided detection (CAD) is proposed to supplement radiologists' interpretation of contrast-enhanced magnetic resonance imaging (MRI) of the breast. MRI of the breast is sometimes used as an alternative to mammography or other screening and diagnostic tests because of its high sensitivity in detecting breast lesions, even among those women—for example, younger women and those with denser breasts—in whom mammography is less accurate. However, MRI has a high false-positive rate because of the difficulty in distinguishing between benign and malignant lesions. It is also used to look for more extensive disease in women diagnosed with breast cancer and to gauge the impact of treatment. Unfortunately, the literature on the use of CAD with MRI of the breast was sparse overall, and few studies addressed the specific situations in which CAD with MRI is used in a clinical setting. A recent TEC Asessment by BCBS found it to be experimental.

http://www.bcbs.com/betterknowledge/tec/vols/21/21_04.html

Deurloo EE, Peterse JL, Rutgers EJ et al. Additional breast lesions in patients eligible for breast-conserving therapy by MRI: impact on preoperative management and potential benefit of computerized analysis. Eur J Cancer 2005;41(10):1393-401

DeMartini WB, Lehman CD, Peacock S et al. Computer-aided detection applied to breast MRI: assessment of CAD-generated enhancement and tumor size in breast cancers before and after neoadjuvant chemotherapy. Acad Radiol 2005;12(7):806-14

Adjuvant chemo for stage 1b breast cancer

Mammographic screening has led to an increase in the number of small, node-negative breast cancers being diagnosed. Node-negative breast cancers that are  1 cm are stage T1a,bN0M0. Controversy surrounds the prognosis of these patients with locoregional therapy only and the need for adjuvant systemic therapy.

Early studies reported 10-year relapse-free survival (RFS) rates higher than 90% without adjuvant systemic therapy, but some more recent data suggest inferior outcomes. High tumor grade is the most consistent factor associated with poor prognosis. Other adverse prognostic factors are younger age, lymphovascular invasion (LVI), high Ki-67, and larger tumors within the T1a,b subgroup. Patients with high-grade tumors and/or LVI may have 10-year RFS rates of less than 75% in the absence of systemic therapy. The prognostic significance of hormone receptor status is unclear. Current guidelines for the systemic management of early-stage breast cancer differ when applied to stage T1a,bN0M0, reflecting the controversial nature of the issue.

Whether Oncotype can provide a relaible method of making treatment decisions in these pateitns is not known. A phase III trial, Tailorx, is being conducted to answer this question.

O. Hanrahan, A. M. Gonzalez-Angulo, S. H. Giordano, R. Rouzier, K. R. Broglio, G. N. Hortobagyi, and V. Valero
Overall Survival and Cause-Specific Mortality of Patients With Stage T1a,bN0M0 Breast Carcinoma
J. Clin. Oncol., November 1, 2007; 25(31): 4952 - 4960.

Emer O. Hanrahan, Vicente Valero, Ana M. Gonzalez-Angulo, Gabriel N. Hortobagyi
Prognosis and Management of Patients With Node-Negative Invasive Breast Carcinoma That Is 1 cm or Smaller in Size (stage 1; T1a,bN0M0): A Review of the Literature Journal of Clinical Oncology, Vol 24, No 13 (May 1), 2006: pp. 2113-2122

L Mauriac, A Keshaviah, M Debled, H Mouridsen, J. Forbes, B Thurlimann, R Paridaens, A Monnier, I Lang, A Wardley, et al.
Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial
Ann. Onc., May 1, 2007; 18(5): 859 - 867.

Epirubicin Cytoxan followed by Taxotere Herceptin for adjuvant terapy of breast cancer

Since 1998, the standard of care for patients with node-positive breast cancer in the United States and other parts of the world has been treatment with doxorubicin and cyclophosphamide followed by the taxane paclitaxel. Herceptin is added for HER+ disease.  This treatment regimen was based on an intergroup study demonstrating that the addition of paclitaxel to doxorubicin and cyclophosphamide (AC) led to rates of disease-free survival of 70 percent and overall survival of 80 percent at five years, as compared with 65 percent and 77 percent, respectively, for doxorubicin and cyclophosphamide alone, with modest differences in the rate of toxic effects.

Because both docetaxel (Taxotere; Rhône-Pouleuc Rorer, Collegeville, PA) and paclitaxel have substantial non-cross-resistance with anthracyclines and therefore activity in anthracycline-resistant breast cancer, defining their roles in the adjuvant therapy of breast cancer is an area of great interest and active clinical investigation. The results of the adjuvant trials using docetaxel assume a particular importance because of the two taxanes in clinical use at this time, docetaxel may be the more active agent in the treatment of metastatic breast cancer, as demonstrated in the results from phase II and III randomized trials.

There are two substitutions to this standard in this case: Epirubicin for Adrimaycin and Taxoter for Taxol.

Based on the above studies, as well as phase II trials, 82 the NSABP B-30 study was designed to directly compare the sequential regimen of AC followed by docetaxel to the combination of doxorubicin plus docetaxel and to the triple combination of doxorubicin plus docetaxel plus cyclophosphamide. This trial was initiated in 1999 and has accrued more than 4,500 of the 5,300 patients needed. Final results are pending but docetaxela appears so far to be equivalent but perhaps slighly more toxic.

The Breast International Group 02-98 randomized trial tested the effect of incorporating docetaxel into anthracycline-based adjuvant chemotherapy and compared sequential vs concurrent administration of doxorubicin and docetaxel. Incorporating docetaxel into anthracycline-based therapy resulted in an improvement in DFS that was of borderline statistical significance. However, important differences may be related to doxorubicin and docetaxel scheduling, with sequential but not concurrent administration, appearing to produce better DFS than anthracycline-based chemotherapy.

Thus, Taxotere is acceptable to sustitue for Taxol. Herceptin is also now an standard of care part of the adjuvant regimen for node positive disease.

The remaining uestion is whether epirubicin can substitute for adraimycin, a similar but more cardiotoxic drug. It seems that such is the case based on substantial literature.

National Comprehensive Cancer Network (NCCN). Breast cancer. Clinical Practice Guidelines in Oncology -- v2.2005. Jenkintown, PA: NCCN; 2005.

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al.; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659-1672.
Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673-1684.

Ahluwalia M. S., Daw H. A., Noronha V., Martin M., Vogel C., the Breast Cancer International Research Group Adjuvant Docetaxel for Node-Positive Breast Cancer.
N Engl J Med 2005; 353:954-955, Sep 1, 2005

Adjuvant Chemotherapy With Sequential or Concurrent Anthracycline and Docetaxel: Breast International Group 02–98 Randomized Trial
Prudence Francis, John Crown, Angelo Di Leo, Marc Buyse, Ana Balil, Michael Andersson, Bo Nordenskjöld, Istvan Lang, Raimund Jakesz, Daniel Vorobiof, Jorge Gutiérrez, Guy van Hazel, Stella Dolci, Sophie Jamin, Belguendouz Bendahmane, Richard D. Gelber, Aron Goldhirsch, Monica Castiglione-Gertsch, Martine Piccart-Gebhart
On behalf of the BIG 02-98 Collaborative Group Journal of the National Cancer Institute
JNCI Journal of the National Cancer Institute 2008 100(2):121-133;

S. Gluck Adjuvant Chemotherapy for Early Breast Cancer: Optimal Use of Epirubicin
Oncologist, November 1, 2005; 10(10): 780 - 791.
.

Autologous stem cell transplant for follicular lymphoma

Lay Summary:

The role of AuSCT is not entirely clear in follicular lymphoma.

There are now 3 conflicitng studies of autologous transplant for follicular lymphoma.

Despite nearly identical eligibility criteria and the use of an anthracycline-based induction treatment in all studies, the results are quite different. The previous studies found a significant advantage to autologous stem cell transplantation (ASCT). The German Lymphoma Study Group (GLSG) reported that patients randomized to transplantation had a 64.7% progression-free survival (PFS) rate at 5 years versus 33% with conventional chemotherapy. The Groupe Ouest-Est d'Etude des Leucémies aigues et autres Maladies du Sang (GOELAMS) group reported 60% PFS for those randomized to autologous transplantation versus 48% with conventional chemotherapy. By contrast, the Groupe d'Etude des Lymphomes de l'Adulte (

GELA

) study does not show a significant PFS advantage for autologous transplantation.

The overall role of ASCT in follicular lymphoma continues to be debated. It is an excellent treatment option for the management of younger patients with recurrent disease. In advanced newly diagnosed lymphoma, a survival advantage has yet to be shown; with more prolonged follow-up it may still emerge in the GLSG study. An increased risk for therapy-related acute myeloid leukemia (t-AML) was observed in the GLSG and GOELAMS studies, but this risk may be minimized by modulation of induction and mobilization therapy preceding transplantation. Despite spectacular advances since the introduction of rituximab, many patients with advanced disease and a high Follicular Lymphoma International Prognostic Index (FLIPI) score have disease recurrences. For such patients, the continued study of autologous transplantation, possibly in combination with rituximab for in vivo purging, remains an important area of investigation.

In conclusion, there is no consensus regarding autologous stem ell transplantation for follicular lymphoma. Since some experts lukewarmy advocate it, it should not be considered "not medically necessary', even if it is arguably still investigational.

Koen van Besien Autologous transplantation for follicular lymphoma? Not too soon! Blood, 15 October 2006, Vol. 108, No. 8, pp. 2496-2497.

NCCN.ORG

BCR/ABL monitoring of chronic myelogenous leukemia on Gleevec

There  have been no studies that  demonstrate that followup with BCR/ABL assists with actual clinical management of CML. Chronic myeloid leukemia has become a paradigm for the discovery of target therapeutic approaches in the field of onco-hematology. Recognition of the tyrosine kinase activity of the p210Bcr-Abl oncoprotein led to the development of compounds targeting against BCR-ABL and then controlling the leukemic proliferation. Imatinib mesylate, one of the first tyrosine kinase inhibitors developed, was found effective and safe. According to five-years experience with this drug, it is recommended that the golden standard for initial treatment of newly diagnosis chronic myeloid leukemia patients should be 400 mg Imatinib daily.

It is not clear what the best monitoring stategy of imatinib might be. Some physicians get regular bcr/abl analysis, others only use it for monitoring when Ph chromosome is undetectable. As noted, there is no clear consensus on how to use this test. NCCN does recommedn BCR/ABL every three months.

Gluckman, J. Reiffers, et al.
Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years
Blood, January 1, 2007; 109(1): 58 - 60.

J. V. Melo, T. P. Hughes, and J. F. Apperley
Chronic Myeloid Leukemia
Hematology, January 1, 2003; 2003(1): 132 - 152.

Hematology Disease Site Group. Walker I, Makarski J, Stevens A, Meyer RM. Treatment of chronic myeloid leukemia with imatinib. Toronto (ON): Cancer Care Ontario (CCO); 2004 Jul 16. 27 p. (Practice guideline report; no. 6-15). [39 references]

http://www.cdhb.govt.nz/chlabs/miscdocuments/CML_Monitoring_Guidelines_Jul%202007.pdf