History Of Chronic Myelogenous Leukemia Research Articles

Three cases of uncommon medication‐associated osteonecrosis of temporal bone

AbstractIntroductionMedication‐related osteonecrosis of the temporal bone is rare and has been reported to be associated with the use of anti‐resorptive and biologic agents. Here, we present the first case of tyrosine‐kinase inhibitor‐related external auditory canal (EAC) osteonecrosis as well as two cases related to anti‐resorptive therapies.MethodsA retrospective case series.ResultsCase one: an 84‐year‐old female presented with chronic otitis externa and osteonecrosis of EACs bilaterally. She had a history of osteoporosis treated with denosumab and risedronic acid. She successfully underwent left EAC reconstruction using an inferiorly‐based pedicle periosteal flap while the right ear canal was managed conservatively. Case two: a 69‐year‐old male presented with osteonecrosis of the right EAC. He had a history of osteoporosis treated with alendronic acid and zoledronic acid. His osteonecrosis is conservatively managed with local debridement and antibiotic application. Case three: a 60‐year‐old male presented with osteonecrosis of the right inferior EAC. He had a history of chronic myelogenous leukemia treated with a tyrosine‐kinase inhibitor, imatinib. After failing conservative therapy, he underwent right ear canal reconstruction using a periosteal vascular pedicle flap without complication and experienced complete resolution to his symptoms.ConclusionAnti‐resorptive agents and/or tyrosine kinase inhibitors may lead to dysregulation of bone remodeling and result in rare cases of temporal bone osteonecrosis. When a local debridement and antibiotic therapy fail, definitive surgical excision of necrotic bone with subsequent reconstruction of the EAC may offer patients a possible resolution in symptoms.

A Case Report of Successful Kidney Transplantation in a Patient With Chronic Myelogenous Leukemia (CML) Who Has Been in Remission for 15 Years on Imatinib

For chronic myeloid leukemia (CML), a Philadelphia chromosome-positive myeloproliferative neoplasm, the introduction of tyrosine kinase inhibitors has transformed CML from a lethal disease into a manageable chronic disease with a close-to-normal life expectancy. Active malignancy is an absolute contraindication to kidney transplantation. However, it is controversial whether kidney transplantation can be safely performed in patients with a history of CML who are in remission. We describe the clinical course of a 64-year-old male patient with chronic kidney disease from diabetic nephropathy (DMN) who underwent living donor kidney transplantation. The patient was diagnosed with CML 15 years ago and promptly achieved cytogenetic and molecular biological remission after starting imatinib. After that, he continued imatinib treatment for 15 years and was in remission, but his chronic kidney disease from DMN gradually worsened. A preemptive living donor kidney transplant was performed in July 2020. Imatinib for CML was discontinued because the patient maintained deep molecular remission (DMR) of major molecular response for more than 15 years before kidney transplantation. After kidney transplantation, the transplanted kidney function remained good at approximate serum creatinine levels of 1.1 mg/dL without histopathologic rejection, and the 3 monthly BCR-ABL1 measurement results were negative and are in progress. Thus, he continues to maintain treatment-free remission status without imatinib for 26 months after renal transplantation. In conclusion, this result suggests that CML with long-lasting DMR on imatinib therapy can be considered an inactive malignancy and therefore a relative indication for kidney transplantation.

SALMONELLA ENTERITIDIS BACTEREMIA AND EMPYEMA FORMATION

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Nontyphoidal Salmonellae are anaerobic gram-negative bacilli that most commonly present with gastroenteritis but can cause extra-intestinal manifestations such as bacteremia, osteomyelitis, septic arthritis, endocarditis, endovascular infections, and abscesses. They have rarely been implicated in pulmonary infections. Here we describe a patient with chronic pleural effusions who had Salmonella enteritidis bacteremia and subsequent development of an empyema. CASE PRESENTATION: A 52 year-old male with history of chronic myelogenous leukemia (CML) who has been on dasatinib for the past 8 years, initially presented with fever, abdominal pain, and watery diarrhea. He was found to have Salmonella enteritidis bacteremia, improved with IV Ceftriaxone, and was discharged with a 10 day oral Cefdinir course. A CT abdomen/pelvis done during this admission was negative for intra-abdominal pathology but did note bilateral pleural effusions. He then presented one month later with cough, shortness of breath, and left-sided pleuritic chest pain. He was found to be hypoxic with labs significant for leukocytosis to 33 x10^9/L. CT chest revealed a large left pleural effusion with septations and pleural enhancement concerning for an empyema. Diagnostic thoracentesis was performed with drainage of purulent fluid and cultures subsequently growing Salmonella enteritidis. He underwent VATS which revealed a complex multiloculated empyema entrapping the entire left hemithorax, dense adhesions between the lung and the mediastinum, chest wall, and diaphragm, and a thick fibrous peel entrapping the left lung. Complete open decortication was performed, and a chest tube was placed. He improved clinically and was started on Ciprofloxacin for prolonged course. DISCUSSION: This patient initially presented with acute gastroenteritis due to Salmonella enteritidis, developed secondary bacteremia, and was treated with appropriate antibiotics. He later presented with dyspnea and cough with imaging concerning for a loculated pleural effusion and empyema. This was in the setting of chronic benign transudative pleural effusions likely secondary to his dasatinib therapy. This effusion was likely seeded when he was bacteremic, leading to development of an empyema. His history of malignancy and chronic lymphopenia likely also predisposed him to severe extraintestinal Salmonella infection given his impaired cellular immunity. CONCLUSIONS: Non-typhi Salmonella are not routinely associated with pleuropulmonary disease but can be a rare cause of empyema. REFERENCE #1: Acheson, D., & Hohmann, E. L. (2001). Nontyphoidal Salmonellosis. Clinical Infectious Diseases, 32(2), 263-269. https://doi.org/10.1086/318457 REFERENCE #2: Pathmanathan, S., Welagedara, S., Dorrington, P., & Sharma, S. (2015). Salmonella empyema: a case report. Pneumonia (Nathan Qld.), 6, 120–124. https://doi.org/10.1007/BF03371465 DISCLOSURES: No relevant relationships by Amy Amornmarn, source=Web Response No relevant relationships by Katherine Gershner, source=Web Response No relevant relationships by Almutasem Hamed, source=Web Response

Benign Pseudoglandular Mesothelial Cell Inclusions in Cervical Lymph Nodes of a Patient With Multiple Malignancies: Case Report and Review of Literature

Abstract Mesothelial cell inclusions in cervical lymph nodes are of exceedingly rare occurrence and can be mistaken for metastatic adenocarcinoma. We report the case of a 27-year-old woman with a history of chronic myelogenous leukemia, diagnosed at age 5 years, and a recent diagnosis of alveolar soft part sarcoma of the left parotid gland. The patient underwent a left parotidectomy and neck dissection with intraoperative finding of abnormal lymph nodes in levels II to V. Histological examination revealed clusters of bland cells with pseudoglandular formation in 6 of 14 level IV/V lymph nodes. Immunological stains were consistent with mesothelial origin, and the diagnosis of benign mesothelial cell inclusions was made. Recognition of this entity in the evaluation of lymph nodes is important to prevent misdiagnosis of metastatic disease, particularly in a patient with multiple known malignancies.

Ichthyosiform Pityriasis Rubra Pilaris-Like Eruption Secondary to Ponatinib Therapy: Case Report and Literature Review.

Tyrosine kinase inhibitors have revolutionized the chemotherapy arena as targeted therapies for a multitude of malignancies. They are more selective than conventional chemotherapy, and often elicit fewer systemic adverse events, however toxicities still exist. Cutaneous toxicities are common and their management presents a novel challenge to physicians and patients. Ponatinib is a third-generation tyrosine kinase inhibitor increasingly reported to cause cutaneous eruption. A 50-year-old woman with a history of chronic myelogenous leukemia presented with a 4-month history of worsening atrophic and ichthyosiform pink plaques involving the axillae, thighs and abdomen; red patches were also observed on the cheeks and forehead. She was started on the third-generation, ponatinib, 5 months earlier because of disease refractory to previous therapies including interferon, imatinib, dasatinib and bosutinib. A skin biopsy revealed perifollicular fibrosis, alternating orthokeratosis and parakeratosis, and a sparse perivascular lymphocytic infiltrate consistent with a pityriasis rubra pilaris-like reaction. Topical tretinoin 0.025% cream was initiated, resulting in resolution within 3 weeks without discontinuation of ponatinib. A review of previous reports identified significant similarities among the ponatinib-induced drug reactions. Here, we highlight not only that cutaneous eruptions occur on ponatinib therapy, but that the dermatologic manifestations are characteristic and unique, and benefit from retinoid therapy, without requiring interruption of vital chemotherapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s40800-017-0055-y) contains supplementary material, which is available to authorized users.

New adnexal masses in a patient with a history of chronic myelogenous leukemia: a case report

Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm characterized by abnormal hyperplasia of granulocytes. Though not one of the common signs and symptoms, extramedullary hematopoiesis (EMH) can be associated with CML. Here we report a rare case of extramedullary hematopoietic infiltration of the ovaries in a patient with known CML who presented with rapidly developing adnexal masses.

Economic Impact of Imatinib Mesylate Withdraw: An Option for Third World Countries?

Introduction: The advent of tyrosine kinase inhibitors has changed the natural history of chronic myelogenous leukemia (CML), promoting molecular remission in a high number of patients. In 40-60% of the patients that reach deep molecular responses (RM4.5 or more) and are using imatinib mesylate for 24 months or longer, a molecular response can be maintained after the cessation of the drug. Besides improving life quality in those patients, to withdraw the medication could have a great economic impact in the health system, what is extremely important in third world countries.Objective: To estimate the economic impact of stopping imatinib mesylate in CML chronic phase patients, receiving treatment for at least 36 months and presenting deep molecular response, determinate by BCR-ABL transcripts with quantitative reverse transcriptase polymerase chain reaction (QRT-PCR), in the last 24 months.Patients and methods: A single center observational retrospective study, including all patients diagnosed with chronic phase CML, confirmed by cytogenetic or molecular exams receiving treatment at a tertiary hospital in Brazil. All patients received imatinib mesylate either in first or second line therapy. Patients presenting deep molecular response for at least 24 months, under imatinib mesylate for 36 months or more were considered eligible for discontinuation the drug. The annual coast with the treatment was estimated considering the coasts of the medication and the QRT-PCR molecular exams in the Brazilian public health system.Results: In this study, 169 patients date were analyzed, the median follow up time is 5 years (range 1-13 years), 26 (15%) of those patients are eligible for stopping imatinib mesylate according to the criteria previously mentioned. Considering the requirement of QRT-PCR exams every month in the first year of discotinuating the drug, these patients would coast proximally 1.550,00 dollars/ patients year for the public health system. This coast could be reduced to 800,00 and 520 dollars/patients year, after the second and third year of the medication withdraw, when monitoring molecular response can be done every 2 and 3 months respectively. The patients receiving imatinib mesylate, and having QTR-PCR exams every six months, in the other hand, would coast the Brazilian public health system over 31.000, 00dollars /patients year. Stopping imatinib mesylate could reduce CML chronic phase treatment coasts in up to 95%.Discussion: Discontinuating imatinib mesylate is something that must be done only in clinical trial. The economic impact projection shown in this study observed the eligibility criteria described in the literature. If stopping imatinib mesylate proves to be a safe option, studies promoting it should be done in Brazil and other third world countries, as a manner of saving resources in the health system. Furthermore, the impact in life quality free of adverse effects and the possibility of gestation in young woman is not to be ignored. DisclosuresNo relevant conflicts of interest to declare.

Chromosomal rearrangement involving 11q23 locus in chronic myelogenous leukemia: a rare phenomenon frequently associated with disease progression and poor prognosis.

BackgroundProgression of chronic myelogenous leukemia (CML) is frequently accompanied by cytogenetic evolution, commonly unbalanced chromosomal changes, such as an extra copy of Philadelphia chromosome (Ph), +8, and i(17)(q10). Balanced chromosomal translocations typically found in de novo acute myeloid leukemia occur occasionally in CML, such as inv(3)/t(3;3), t(8;21), t(15;17), and inv(16). Translocations involving the 11q23, a relatively common genetic abnormality in acute leukemia, have been seldom reported in CML. In this study, we explored the prevalence and prognostic role of 11q23 in CML.MethodsWe searched our pathology archives for CML cases diagnosed in our institution from 1998 to present. Cases with 11q23 rearrangements were retrieved. The corresponding clinicopathological data were reviewed.ResultsA total of 2,012 cases of CML with available karyotypes were identified. Ten (0.5%) CML cases had 11q23 rearrangement in Ph-positive cells, including 4 cases of t(9;11), 2 cases of t(11;19), and 1 case each of t(2;11), t(4;11), t(6;11), and t(4;9;11). Eight cases (80%) had other concurrent chromosomal abnormalities. There were 6 men and 4 women with a median age of 50 years (range, 21–70 years) at time of initial diagnosis of CML. 11q23 rearrangement occurred after a median period of 12.5 months (range, 0–172 months): 1 patient in chronic phase, 2 in accelerated phase, and 7 in blast phase. Eight of ten patients died after a median follow-up of 16.5 months (range, 8–186 months) following the initial diagnosis of CML, and a median of 6.7 months (range, 0.8–16.6 months) after the emergence of 11q23 rearrangement. The remaining two patients had complete remission at the last follow-up, 50.2 and 6.9 months, respectively. In addition, we also identified a case with 11q23/t(11;17) in Ph-negative cells in a patient with a history of CML. MLL involvement was tested by fluorescence in situ hybridization in 10 cases, and 7 cases (70%) were positive.ConclusionsIn summary, chromosomal rearrangements involving 11q23 are rare in CML, frequently occurring in blast phase, and are often associated with other cytogenetic abnormalities. These patients had a low response rate to tyrosine kinase inhibitors and a poor prognosis.

Very Late Relapse of Chronic Myelogenous Leukemia Following Stem Cell Transplant

Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm of the bone marrow that is associated with the Philadelphia chromosome, which creates the fusion BCR-ABL tyrosine kinase. Prior to development of tyrosine kinase inhibitors such as imatinib, the standard of care for treatment in certain clinical situations was hematopoietic stem cell transplant. We present a case of a 61 year-old male with a history of CML who received a stem cell transplant 20 years prior. He now had developed an increased white blood cell count and was found to have recurrence of CML in his bone marrow and via peripheral blood analysis for BCR-ABL. Through further evaluation it was found that the recurrence was genetically the same as his original malignancy and not a de novo evolution of his sibling donor graft cells. He was trialed on several tyrosine kinase inhibitors following his diagnosis but had complications with one and progression on another. He was eventually given a donor leukocyte infusion to combat his disease which improved his status and was without complication. This case demonstrates a rare but known entity of very later recurrence of CML following stem cell transplant.

A rare case of subcutaneous Sweet’s syndrome in a patient with chronic myelogenous leukemia: a case report and review of the literature

Subcutaneous Sweet’s syndrome (SS) is a rare variant of classic SS characterized by a neutrophilic infiltrate exclusively or predominantly in the subcutaneous tissue, with minimal or absent dermal involvement. We report the case of a patient with a history of chronic myelogenous leukemia who developed subcutaneous SS. Although it has been described in patients with myelodysplastic syndromes and acute myeloid leukemia, this is the first report, to our knowledge, of this rare entity occurring in the setting of a myeloproliferative disorder.

Overcoming Psychosocial and Developmental Barriers to Blood and Marrow Transplantation (BMT) in an Adolescent/Young Adult (AYA) Transgender Patient with Chronic Myelogenous Leukemia

Adolescents/young adults (AYAs) afflicted with cancer face unique barriers to potentially standard curative therapies, such as blood and marrow transplantation (BMT). Transgender AYAs face additional barriers and there is a dearth of published literature regarding their oncology-related experience. We present the case of an AYA male-to-female (MTF) transgender patient on cross-sex hormone therapy, with a history of Chronic Myelogenous Leukemia (CML) and significant psychosocial barriers, which initially served as a barrier to BMT at two different centers; we modified our standard consent and education process and was able to successfully proceed with BMT and subsequently cure her CML. Despite unique challenges, AYA and transgender patients with significant psychosocial barriers may achieve successful outcomes with BMT. Research is needed regarding guidelines for cross-sex hormone therapy administration for patients undergoing BMT and other issues, which may be unique to the transgender experience.

Conquering cancer in our lifetime: new diagnostic and therapeutic trends.

Cancer has now surpassed cardiovascular disease as the number 1 killer of both men and women (1). Approximately 1 of 3 of us will develop cancer during our lifetime. Despite the war on cancer declared more than 40 years ago by President Richard Nixon, the battle has not yet been won, despite a substantial investment in resources. The US National Cancer Institute has an annual budget of approximately $5 billion and since 1971 has spent >$90 billion on the science, treatment, and prevention of cancer (2). The pharmaceutical industry has invested several times that sum in developing anticancer drugs and antibodies. Small-molecule inhibitors such as imatinib have changed the natural history of chronic myelogenous leukemia and gastrointestinal stromal tumor. Antibodies that include rituximab and trastuzumab have improved overall and long-term survival for patients with lymphoma and breast cancer, but many new targeted agents approved by the US Food and Drug Administration have extended progression-free survival times by only a few months. Of greater concern is that only 1 in 20 new oncologic agents entering clinical trials proves to be sufficiently safe and effective to achieve approval. Progress has been slow and sometimes inefficient. Robert C. Bast, Jr. Some scientists have claimed that the cancer incidence and mortality rates have not changed over the last 15 years. The fact is, however, that the overall cancer mortality rate has declined significantly in the US since 1990, despite the aging of the population. For example, the incidence for the major killer, lung cancer, began to decline in the early 1980s, owing to the antismoking campaigns, and the overall 5-year mortality rate decreased by 1.6% by 2010. …

T(15;17)(q24.1;q21.2)/PML-RARA in blast phase of chronic myelogenous leukemia: a rare form of clonal evolution

Chronic myelogenous leukemia (CML) in blast phase (BP) is frequently accompanied by cytogenetic abnormalities in addition to t(9;22)(q34;q11.2). We describe a 72-year-old woman with a history of CML, treated with imatinib, and in complete remission for 23 months when she developed sudden coagulopathy as a manifestation of BP. Bone marrow (BM) aspiration and biopsy revealed hypercellular BM with numerous promyelocytes with cytochemical analysis of a BM aspirate smear showing strong myelokperoxidase positivity. Auer rods were also identified. Conventional cytogenetic analysis showed 46,XX,der(3)t(3;15)(q21;q15)t(15;17)(q24.1;q21.2),t(9;22)(q34;q11.2),der(15)t(3;15),del(17)(q21)[20]. The presence of BCR-ABL1 and PML-RARA were confirmed by fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). Molecular studies showed no mutations in ABL1, FLT3, NPM1, RAS, KIT, IDH1, IDH2, and JAK2 genes. The patient was treated with all-trans retinoic acid and arsenic trioxide and achieved complete cytogenetic remission with no evidence of PML-RARA detected by FISH and RT-PCR and low level of BCR-ABL1 fusion transcripts detected by RT-PCR. The patient expired as a result of multiorgan system failure 2 months later. Based on our review of the literature, this is the second confirmed case of CML developing t(15;17)(q24.1;q21.2)/PML-RARA at time of BP. Although the BP resembled de novo acute promyelocytic leukemia (APL) morphologically, this patient had a more aggressive clinical course (compared with de novo APL) and died of complications of therapy.

Clinical Significance of Mixed Phenotype in Adult Patients with Philadelphia Chromosome-Positive Acute Leukemia–no Prognostic Impact in the Imatinib Era.

Abstract 2574 Background:Mixed phenotype acute leukemia (MPAL) has historically been known as biphenotypic acute leukemia (BAL), and novel diagnostic criteria for this disease entity are described in the World Health Organization (WHO) classification 4th edition. As the most common recurrent genetic abnormality observed in MPAL is the bcr-abl fusion gene, Philadelphia chromosome-positive MPAL (Ph+MPAL) has been recognized as one distinctive disease entity. The prognosis of Ph+B-cell acute lymphoblastic leukemia (Ph+B-ALL) has been dramatically improved with the introduction of imatinib, and the goal of this study was to determine whether imatinib results in a survival benefit in the context of Ph+MPAL. Patients and Methods:We retrospectively analyzed 42 consecutive adult patients who were diagnosed with Ph+AL between January 2001 and March 2012 at Gunma University Hospital and Saiseikai Maebashi Hospital in Gunma, Japan. Ph+AL was diagnosed based on detection of the bcr-abl fusion gene with the polymerase chain reaction method and the presence of more than 20% of blasts in the peripheral blood and/or bone marrow. Patients with a previous history of chronic myelogenous leukemia were excluded. The lineage of leukemia cells was defined according to the WHO classification 4th edition. All patients received intensive chemotherapy and concurrent administration of imatinib. The c2-test was used for comparison of binary variables. The Mann-Whitney U test was used for comparison of continuous variables. Overall survival (OS) rate was estimated by the Kaplan-Meier method and were compared using the log-rank test. P < 0.05 was considered as statistically significant. Results:According to the WHO classification 4th edition, 13 (31%) patients were categorized as Ph+MPAL (positive for both myeloid and B-cell lineage), 27 (64%) patients were categorized as B-cell lineage acute lymphoblastic leukemia (Ph+B-ALL), and two (5%) patients were categorized as acute myeloid leukemia (Ph+AML). Patients with Ph+AML were excluded from this study, as the number of patients was relatively small. Of the 40 Ph+AL patients, 23 patients were men, and 17 were women, and the median age was 53 years (range, 16–75 years). Age, sex, white blood cell counts, lactate dehydrogenase levels, and the prevalence of additional cytogenetic abnormalities at diagnosis were not significantly different when comparing the groups, although patients with Ph+MPAL showed significantly higher frequency of major bcr-abl gene than those with Ph+B-ALL (69% and 19%, respectively; p < 0.01). Immunophenotypic analysis revealed that Ph+MPAL patients expressed CD10 and CD34 with significantly lower frequency than Ph+B-ALL patients. Notably, positivity of myeloid antigens (CD13 and 33) was similar between both groups. The complete response (CR) rates after the initial induction therapy were not significantly different when comparing Ph+MPAL and Ph+B-ALL (100% vs. 85%, respectively, p = 0.14). Likewise, the 5-year-OS rate was similar when comparing patients with Ph+MPAL and Ph+B-ALL (55% vs. 53%, respectively, p = 0.87). Of the 13 patients with Ph+MPAL, six patients received AML-type chemotherapy, and seven patients received ALL-type chemotherapy as the initial induction therapy. All patients achieved CR after the initial induction therapy, and there was no significant difference in 5-year OS according to the therapeutic strategy (AML-type vs. ALL-type), (50% vs. 63%, respectively, p = 0.71). Among 12 patients younger than 65 years old who were alive at >3 months after the diagnosis, eight patients underwent allogeneic hematopoietic stem cell transplantation (allo SCT). The 5-year OS was significantly better for patients who underwent allo-SCT than for those who received chemotherapy alone (58% vs. 20%, respectively, p = 0.05). Conclusion:Among adult Ph+AL patients, mixed phenotype was more frequently observed than expected, and Ph+MPAL patients showed unique clinical features, including immunophenotype and the type of bcr-abl fusion gene. Although BAL has been considered as a negative prognostic factor, Ph+MPAL patients showed comparable prognosis to those with Ph+B-ALL who received imatinib-containing intensive chemotherapy. Therefore, the established theory that mixed phenotype is associated with poor outcomes should be revisited among these patients. Disclosures:No relevant conflicts of interest to declare.

The first case of Philadelphia chromosome-negative acute promyelocytic leukemia following imatinib for chronic myelogenous leukemia

In chronic myelogenous leukemia, chromosomal abnormalities in Philadelphia-negative cells are rare and usually transient, but can infrequently lead to myelodysplastic syndrome and/or acute myeloid leukemia. We report an 82-ear-old patient with an 11-year history of chronic myelogenous leukemia, in complete cytogenetic response, who developed Philadelphia-negative t(15;17)/PMLRARA acute promyelocytic leukemia. This isolated case reaffirms several important clinicopathologic and biologic aspects of chronic myelogenous leukemia, and sheds a unique light on its Philadelphia-negative hematopoiesis. It also underlines the importance of continued cytogenetic monitoring of patients in complete cytogenetic response for the emergence of new chromosomal abnormalities.

Development of lichen sclerosus et atrophicus while receiving a therapeutic dose of imatinib mesylate for chronic myelogenous leukemia

Imatinib mesylate (Gleevec) is a selective Bcr-Abl protein tyrosine-kinase inhibitor, and it also inhibits the receptor tyrosine kinases for stem cell factor (c-kit) and platelet-derived growth factor (PDGFR). It is being investigated for use in the treatment of sclerosing dermatoses. A 44-year-old woman with a history of chronic myelogenous leukemia (CML) was referred for the evaluation of a pruritic eruption that developed over 6 months. Examination revealed atrophic plaques confined to the groin, vulva, axillae, inframammary region, trunk, antecubital and popliteal fossae, and posterior thighs bilaterally. A biopsy showed lichen sclerosus et atrophicus (LSetA). At the time of presentation, the patient was receiving imatinib mesylate 400 mg daily for CML. This is the first report of development of LSetA, a sclerosing dermatosis, while receiving a therapeutic dose of imatinib mesylate, a drug thought to have anti-sclerotic properties.

New agents in the treatment of chronic myelogenous leukemia.

The discovery of molecularly targeted agents that selectively inhibit bcr-abl tyrosine kinase activity, such as imatinib, has revolutionized the treatment and natural history of chronic myelogenous leukemia (CML). Treatment of chronic-phase CML with imatinib showed complete cytogenetic response rates of more than 40% in patients after failure of interferon-alpha, and more than 80% in patients with newly diagnosed CML. Patients with CML can now expect excellent long-term survival, often without major side effects. In most patients, however, residual leukemic burden remains detectable using a sensitive reverse transcription-polymerase chain reaction method. In addition, many patients undergoing imatinib therapy will either not respond or lose their response over time because of resistance or intolerance. The introduction of second-generation tyrosine kinase inhibitors (TKIs) re-establishes response in approximately half of these patients. Several agents are being developed for treating patients who experience suboptimal response to second-generation TKIs and for those who develop resistance caused by the emergence of highly resistant BCR-ABL1 mutations. This article provides an overview of novel targeted agents available for CML.

Imatinib Mesylate Induced Gastric B-Cell Lymphoma

Purpose: Imatinib mesylate is a common first-line treatment for chronic myelogenous leukemia (CML). We present the first case, to our knowledge, of a CML patient treated with imatinib mesylate who developed gastric lymphoma. A 53-year-old man with a history of CML was taking imatinib mesylate with confirmed hematological and cytogenetic remission. However, the patient developed diffuse abdominal pain with associated bloody stools. A colonoscopy done 5-years previously showed only hemorrhoids and a benign colon polyp. An esophagogastroduodenoscopy (EGD) done during the same time showed gastric erythema and erosive duodenitis. A new outpatient EGD showed a large, fungating, non-circumferential mass at the incisura (Figure A). The patient had a laparoscopic abdominal exploration which showed a large gastric mass in the body of the stomach, extending into the antrum midway between the lesser and greater curvature. The mass was not removed surgically. In situ staining for Epstein Barr Virus (EBV) confirmed high-grade Burkitt's gastric lymphoma. Fluorescence in situ hybridization (FISH) of the biopsy revealed a genetically distinct neoplasm from CML. Imatinib mesylate was stopped and he received a different chemotherapy regimen for two courses. Follow-up EGD two months later showed only a large gastric ulcer at incisura angularis (Figure B); the mass dramatically decreased in size. Imatinib mesylate, a tyrosine kinase inhibitor, is a first-line chemotherapy agent used in the treatment of CML. It acts to inhibit the tyrosine kinase activity of this disease. The development of a de novo lymphoma and cutaneous EBV-positive B-cell lymphoproliferative disease in CML patients treated by imatinib have been reported, but it is very uncommon. In this case, the EBV gastric lymphoma occurred during imatinib treatment and resolved significantly after stopping treatment; it is thought the modulation of T-cell function by imatinib was the fulcrum point in the development of EBV-gastric lymphoma. In addition, the CML showed genetic and hematological remission, so the concern of a blast crisis forming was mitigated. To our knowledge, this is the first report of gastrointestinal Burkitt's lymphoma development after prolonged treatment with imatinib mesylate and is an important complication of therapy in CML.Figure A: Burkitt's lymphoma seen in stomach Figure B. Reduction of Burkitt's lymphoma in stomach.

Hydroxyurea-induced ulcers on the leg

A 73-year-old man with a history of chronic myelogenous leukemia presented with multiple ulcers on both legs ([Figure 1][1]). The ulcers were extremely painful. The patient had no history of diabetes or hypertension. His ankle–brachial index was normal. The leukemia had been treated for 3 years

Sudden Extramedullary T-Lymphoblastic Blast Crisis in Chronic Myelogenous Leukemia

Imatinib has dramatically altered the natural history of chronic myelogenous leukemia (CML), with the majority of patients now experiencing long-term remission and improved survival. However, in addition to the well-described phenomenon of resistance to imatinib, typically due to point mutations, uncommon consequences (eg, the development of Philadelphia chromosome-negative clones) may infrequently occur. We report 2 cases of sudden BCR/ABL1+ blast crisis in patients with CML who had achieved complete hematologic remission with imatinib therapy but were obligated to discontinue therapy owing to pancytopenia. These sudden blast crises were unusual at 3 levels: first, they were of precursor T lymphoblastic lineage; second, they had a primary extranodal presentation without overt bone marrow involvement; and third, they developed after recent cessation of imatinib. These observations suggest that the occurrence of 2 such rare cases in a single institution within a 1-year time frame may reflect another unusual consequence of imatinib therapy.