Infections in patients on BCR-ABL tyrosine kinase inhibitor therapy: cases and review of the literature.

The introduction of BCR-ABL-tyrosine kinase inhibitors (TKI) for treatment of hematologic malignancies has made a significant impact on patient outcome. Contingent upon their targeted and off-target activity, therapy-associated infectious complications may occur. We present a case of cytomegalovirus pneumonitis and a case of adenovirus hemorrhagic cystitis in two patients with Philadelphia chromosome-positive acute lymphoblastic leukemia on BCR-ABL TKI treatment and review the literature to summarize the infectious complications based on clinical data. As life-threatening infections may occur, treating physicians should maintain a heightened awareness in patients treated with BCR-ABL TKIs. Based on the frequent reports of hepatitis B virus (HBV) reactivation under the treatment BCR-ABL TKIs, screening for and prophylactic therapy of chronic HBV infection should be considered. Similarly, patients would benefit from screening for and treatment of latent tuberculosis.

Long-term survival of patients with resistant lymphoma treated with tandem stem cell transplant.

Dose-intensive chemotherapy with autologous stem cell support is commonly used in resistant/refractory cases of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). The purpose of this study was to evaluate the role of tandem transplantation in these patients. We used non cross-resistant conditioning regimens with thiotepa, mitoxantrone and carboplatin (TMJ) followed by ifosphamide, carboplatin and etoposide (ICE) with autologous stem cell rescue in an attempt to maximize dose intensity and achieve long-term remission. Seventy-six patients were included in this study. Twenty-nine patients with HD and 47 with NHL underwent autologous stem cell transplant using TMJ as the conditioning regimen for the first transplant. Of these, 49 patients proceeded to the second transplant using ICE as the conditioning regimen. In 57 patients, only peripheral blood cells were used and in 11 patients both bone marrow and peripheral stem cells were used. Twelve patients died due to treatment-related toxicity. On an intent to treat basis, 32.14% of patients with HD refractory to initial or subsequent therapy survived long term as opposed to 12.76% of patients with NHL. With a median follow-up of 83 months (range 25 - 110 months), the median disease-free survival of patients with HD was 7 months, as opposed to 2 months for patients with NHL. Multivariate analysis identified that patients with HD had a superior outcome if they were less than 35 years of age and did not have B symptoms. Dose-intensive chemotherapy with tandem transplantation is an option in patients with resistant/refractory lymphoma who have very limited treatment options and poor prognosis.

High dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ) followed by autologous stem cell support in 100 consecutive lymphoma patients in a single centre: analysis of efficacy, toxicity and prognostic factors.

High dose chemotherapy with autologous stem cell transplant is often used in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) who either do not respond to, or relapse after conventional chemotherapy. There is no consensus on the "ideal" pretransplant conditioning regimen. In this study, we analyzed the results of 100 consecutive patients with HD and NHL who met our eligibility criteria and underwent autologous stem cell transplant at New York Medical College and Zalmen A. Arlin Cancer Institute. All patients received high dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ). One hundred patients, 37 with HD and 63 with NHL underwent autologous stem cell transplant using TMJ as a conditioning regimen. All patients with HD had chemo-sensitive relapse while 50 patients with NHL had chemo-sensitive relapse and 13 patients had first complete remission. The source of stem cells was bone marrow (18 patients), peripheral blood (50 patients) and both bone marrow and peripheral blood (32 patients). With a median follow up of 91 months (range 23-147 months), the median survival of patients with HD and NHL who underwent autologous stem cell transplant is 107 months and the 5 years disease free survival is 43%. Median survival of patients with HD and NHL is 87 and 107 months respectively. There were 4 transplant related deaths. Median survival of patients who had sensitive relapse at the time of transplant is 87 months while median survival has not been reached for patients who had first complete remission at the time of transplant. Multivariate analysis identified age>35 years (P=0.02) as a predictor for poor survival for the whole group as well as for patients with NHL (P=0.04). TMJ is a safe and effective regimen when used as a part of autologous stem cell transplant for patients with HD and NHL.

In vivo and in vitro studies on Anaplasma phagocytophilum infection of the myeloid cells of a patient with chronic myelogenous leukaemia and human granulocytic ehrlichiosis.

AIMS: The occurrence of human granulocytic ehrlichiosis (HGE) in a patient with chronic myelogenous leukaemia (CML) provided an opportunity to study whether Anaplasma phagocytophilum, the aetiological agent of HGE, infects mature or immature cells, both in vivo and in vitro. METHODS: Diagnosis of HGE was confirmed by culture, polymerase chain reaction (PCR), detection of intragranulocytic inclusions, and serology. The infection rates of different myelogenous stages of granulocytic differentiation were determined by microscopy. Anaplasma phagocytophilum infection of the bone marrow was analysed by PCR, culture, and microscopy. In addition, the in vitro growth of A phagocytophilum in the patient's granulocytes and in HL-60 cells (a promyelocytic leukaemia cell line) was compared. RESULTS: Pretreatment blood smears showed that mature granulocytic cells had a higher infection rate with A phagocytophilum than did immature cells. In the original inoculation of the patient's cells into HL-60 cells to isolate A phagocytophilum, the bacterium grew faster in the patient's leukaemic cells than in HL-60 cells. Anaplasma phagocytophilum inclusions were rarely seen in bone marrow granulocytes and PCR was negative. In vitro, two A phagocytophilum isolates grew faster in the patient's granulocytes than in HL-60 cells. CONCLUSIONS: The superior growth in CML cells compared with HL-60 cells suggests that A phagocytophilum preferentially infects mature granulocytes. The higher infection rate of the patient's mature versus immature granulocytes before treatment and the minimal level of infection of the patient's bone marrow support this. It is possible that the primary site of infection in HGE is the peripheral mature granulocytic population.

Treatment of relapsed or refractory acute myeloid leukemia with humanized anti-CD33 monoclonal antibody HuM195.

HuM195 is a humanized, unconjugated, anti-CD33 monoclonal antibody. Fifty adult patients with relapsed or refractory AML were randomized to receive HuM195 at a dose of 12 or 36 mg/m(2) by intravenous infusion over 4 h on days 1-4 and 15-18. Patients with stable or responding disease received two additional cycles on days 29-32 and 43-46. HuM195 was given as first salvage therapy in 24 patients and as second or subsequent salvage therapy in 26 patients. Pretreatment blast percentage in the marrow was between 5 and 30% in 20 patients with the others having blast counts greater than 30%. The median age of patients was 62 years (range 26-86) and CD33 was detected in 95% of patients for whom immunophenotyping was available. Of 49 evaluable patients, two complete and one partial remission were observed. All three responses were in patients treated at the 12 mg/m(2) dose level and all had baseline blast percentages less than 30%. Decreases in blast counts ranging from 30 to 74% were seen in nine additional patients. Infusion-related events of fever and chills occurred in the majority of patients and were generally mild and primarily related to the first dose of antibody. No hepatic, renal or cardiac toxicities were observed and other adverse events such as nausea, vomiting, mucositis and diarrhea were uncommon or felt to be unrelated to HuM195. In addition, anti-HuM195 responses were not detected. HuM195 as a single agent has minimal, but observable, anti-leukemic activity in patients with relapsed or refractory AML and activity is confined to patients with low burden disease. No significant differences in clinical efficacy or toxicity were seen between the two dose levels of antibody. HuM195 was well tolerated with infusion-related fevers and chills the predominant toxicities seen. Meaningful clinical efficacy of this unconjugated monoclonal antibody may be realized only in patients with minimal residual disease, or in combination with chemotherapy.

Efficacy and safety of gemtuzumab ozogamicin in patients with poor-prognosis acute myeloid leukemia.

The objective of this work was to determine the safety and efficacy of gemtuzumab ozogamicin in patients with poor prognosis acute myeloid leukemia (AML). Patients with the following diagnoses/characteristics were treated with 1-3 infusions of gemtuzumab ozogamicin at a dose of 9 mg/m2: (1) relapse of AML < or = 6 months of first complete remission (CR); (2) AML refractory to chemotherapy at initial induction or at first relapse; (3) AML in second or greater relapse; (4) myeloid blast crisis of chronic myeloid leukemia (CML); (5) untreated patients > or = 70 years or > or = 55 years with abnormal cytogenetics (excluding inv 16, t(15;17) and t(8;21)) and/or an antecedent hematologic disorder; (6) refractory anemia with excess blasts in transformation (RAEBT). Forty-three patients, ages 19-84 (mean 62), were treated, including 7 patients with untreated AML age > 70 years, 2 with untreated RAEBT, 14 with AML first salvage (first remission 0-6 months), 15 with AML > or = second salvage and 14 with myeloid blast phase of CML. The overall response rate was 14%, with 4/43 (9%) patients achieving CR and 2/43 (5%) achieving CR without platelet recovery. The most significant toxicity was neutropenic fever, which occurred in 84% of patients. In conclusion, in patients with relapsed/refractory AML, gemtuzumab ozogamicin has a comparable response rate to single-agent chemotherapy and may offer a more favorable toxicity profile.

Intravenous bolus topotecan in patients with myelodysplastic syndrome.

We treated 16 patients with myelodysplastic syndromes with 24 courses of bolus topotecan. Patients received topotecan as a daily 15 minute infusion for 5 days at 3 dose levels (4.0 mg/m2/d, 2.0 mg/m2/d or 2.5 mg/m2/d). There was one complete response and one partial response (overall response rate 12%). Toxicity included myelosuppression, diarrhea, ileus and mucositis. There were 3 treatment-related deaths. The results of this schedule of topotecan appeared to be inferior to that reported with infusional topotecan in patients with MDS.

Secondary acute myelogenous leukemia and myelodysplasia without abnormalities of chromosome 11q23 following treatment of acute leukemia with topoisomerase II-based chemotherapy.

Therapy-related MDS and AML are complications of intensive chemotherapy regimens. Traditionally, patients exposed to topoisomerase II inhibitors are reported to develop secondary AML with abnormalities of chromosome 11q23. We evaluated the long-term hematologic toxicity of topoisomerase II-intensive high-dose mitoxantrone-based chemotherapy in 163 newly diagnosed acute leukemia patients treated over an 8 year period. Nine (5.5%) patients developed new cytogenetic abnormalities. Four patients developed MDS with progression to AML, three patients developed new abnormalities at the time of relapse, and three patients (including one of the former patients) had changes that were not associated with hematologic disease. The abnormalities most frequently involved chromosomes 7q, 20q, 1q, and 13q. Despite the use of topoisomerase II-intensive treatment, no patient developed an abnormality involving chromosome 11q23. Spontaneous resolution of some changes and prolonged persistence of others in the absence of hematologic disease indicates that some cytogenetic changes are not sufficient to promote leukemogenesis.

Evaluation of topotecan and etoposide for non-Hodgkin lymphoma: correlation of topoisomerase-DNA complex formation with clinical response.

BACKGROUND: Topotecan, a topoisomerase I inhibitor, acts by stabilizing the topoisomerase DNA cleavage complex. Etoposide, a topoisomerase II inhibitor, mediates antitumor activity by stabilizing cleavage complex formed between topoisomerase II and DNA. These two agents have therapeutic activity in non-Hodgkin lymphoma. The authors report Phase I data of topotecan and etoposide combination for patients with recurrent or refractory non-Hodgkin lymphoma and correlation of topoisomerase-DNA complex formation to clinical response. METHODS: Twenty-two patients with recurrent or refractory aggressive non-Hodgkin lymphoma were treated at four dose levels of topotecan (1 mg/m(2)/day to 2.5 mg/m(2)/day). Topotecan was given at a 30-minute infusion daily with etoposide 150 mg/m(2)/day, both for 5 days. Topoisomerase-DNA covalent complex formation was measured using in vivo link assay, whereas topoisomerase I, IIalpha, and IIbeta in RNA expression levels were determined by reverse transcription-polymerase chain reaction in blood samples. The relation of these levels to clinical response was studied. RESULTS: The maximum tolerated dose of topotecan was 2.0 mg/m(2)/day for 5 days. Oropharyngeal mucositis was dose-limiting. Of 21 examinable patients, 3 patients achieved complete remission, and 5 patients achieved partial remission. Of six untreated patients who experienced a recurrence, three had complete remission, and the other three had partial remission. Drug-induced topoisomerase-DNA complex formation was observed throughout the treatment in blood samples of all the patients who responded. However, only 4 of 13 patients, who did not respond, formed covalent complex at all time points. This was statistically significant (P = 0.024). In all patients, expression levels of topoisomerase I and IIbeta mRNA remained similar to pretreatment levels, whereas topoisomerase IIalpha mRNA levels decreased dramatically by the third day. CONCLUSION: The recommended Phase II dose of topotecan with etoposide of 150 mg/m(2)/day for 5 days was 2.0 mg/m(2)/day for 5 days. Topoisomerase-DNA complex formation correlated with response to treatment.

Cardiovascular considerations with anthracycline use in patients with cancer.

Anthracyclines are important chemotherapeutic agents that are used for the treatment of various malignancies in both adults and children, but their usefulness has been limited by cardiotoxicity that is usually dose related. Oxidative injury appears to be the cause of myocardial dysfunction when using these drugs. Screening for early myocardial injury with troponin testing, echocardiography, and radionuclide examinations has reduced the incidence of chronic cardiac dysfunction. Various anthracycline analogues have been developed that have less cardiotoxicity. Dexrazoxane, an iron chelator, and the radioprotective agent amifostine protect against cardiac injury, thus allowing the use of higher doses of anthracyclines. Other strategies that have been evaluated are dietary glutamine supplementation and the use of the antioxidant probucol.

Phase II evaluation of a high-dose mitoxantrone based induction regimen in untreated adults with acute myeloid leukemia.

To evaluate a regimen including high-dose mitoxantrone in previously untreated adults with AML, 45 patients aged 21-59 (median 41) were given cytarabine, 3 g/m2 days 1-5, mitoxantrone, 80 mg/m2 day 2 and etoposide, 150 mg/m2 days 1,3,5. Post-remission therapy consisted of 5 cycles combining the same agents at reduced doses. Complete remission was seen in 36 patients. The observed 3-year survival is 28%. Cytogenetic pattern and CD34 expression correlated with response and survival. Significant toxicity included myelosuppression, mucositis, diarrhea and hyperbilirubinemia. Ventricular ejection fraction was generally reduced, with clinical cardiac dysfunction in only 2 patients. This high-dose mitoxantrone combination can be administered to young adults with AML with tolerable toxicity and results comparable to those of other dose-intensive regimens.

High-dose chemotherapy and stem cell transplantation for patients with stage IV breast cancer without clinically evident disease: correlation of CD34+ selection to clinical outcome.

Forty-five patients with metastatic breast cancer without clinically evident disease were treated with thiotepa 750 mg/m2, mitoxantrone 40 mg/m2 and carboplatin 1000 mg/m2 followed by stem cell transplantation to determine the safety and efficacy of CD34+ selection of peripheral blood stem cells. Of these, 15 patients' (group I) stem cells were processed through Baxter Isolex 300 device for CD34+ selection, whereas 30 patients (group II) received unmanipulated stem cells. Toxicity, progression-free survival and survival were compared between these two groups. There was no difference in transfusion requirements, white cell count and platelet recovery and non-hematologic toxicity between the two groups. The survival of patients in group I was 27 months compared to 38 months in group II (P = 0.8). The progression-free survival was 12 months and 13.5 months for group I and group II patients, respectively (P = 0.6). Our results indicate that while there is no adverse effect, there is also no significant advantage of CD34+ selection in terms of progression-free survival and survival in patients with metastatic breast cancer without clinically evident disease. Bone Marrow Transplantation (2000).

Clinical and laboratory evaluation of all-trans retinoic acid modulation of chemotherapy in patients with acute myelogenous leukaemia.

All-trans retinoic acid (ATRA) is synergistic with chemotherapy in leukaemia cell lines. We treated 53 patients with newly diagnosed acute myelogenous leukaemia (AML) with high-dose cytarabine-based chemotherapy followed by ATRA. Peripheral blood and bone marrow samples were obtained to study the effect of in vitro exposure to ATRA and to measure apoptosis and bcl-2. The response rate was 72% for patients under age 60 years and 46% for patients aged 60 years or above. There was no difference in the percentage of responding patients, time to recurrence or overall survival for patients receiving chemotherapy with ATRA vs. historical controls receiving chemotherapy without ATRA. After in vitro exposure of day 3 bone marrow samples to ATRA, there was an increase in apoptotic cells in 25% of patient samples compared with samples not exposed to ATRA. Later date of peak apoptosis in peripheral blood and higher percentage of apoptotic cells in bone marrow on day 3 of treatment were associated with lack of clinical response to treatment. Increased bcl-2 in patient samples was associated with shorter time to recurrence and poor cytogenetic risk. The addition of ATRA to chemotherapy did not improve patient outcome. However, evidence of in vitro response to ATRA in 25% of patients suggests that retinoid pathways should be studied further in patients with AML.

Cyclosporine-induced autologous graft-versus-host disease in patients with acute myeloid leukemia undergoing non-myeloablative chemotherapy without progenitor cell reinfusion.

To determine the incidence and severity of cyclosporine-induced graft-versus-host disease following non-myeloablative chemotherapy without progenitor cell reinfusion in patients with acute leukemia, 17 adults with refractory acute myeloid leukemia (14) or blastic phase of chronic myeloid leukemia (3) were treated with etoposide 2400 mg/m2 and cyclophosphamide 120 mg/kg followed by cyclosporine (CsA) 2.5 mg/kg i.v. daily and interferon gamma 0.025 mg/m2 subcutaneously every other day until day 28. Skin biopsies were obtained on days 14 and 28, or on the appearance of a skin rash, and graded for GVHD. Blood samples were examined at baseline and weekly starting on day 14 for natural killer (NK) cell and T cell lymphocytic changes. Post-treatment lymphocytes from select patients were assessed for allogeneic NK cell and autologous leukemic cell cytolytic activity. Four patients developed pathologic grade 2 cutaneous acute GVHD. Of the three patients who achieved a complete remission, two had evidence of GVHD. Post-treatment, three patients (two with GVHD) in whom adequate numbers of lymphocytes could be obtained showed NK cell cytolytic activity against allogeneic tumor cells (K562), but none had cytolytic activity against their own cryopreserved leukemic cells. These data suggest that in patients with AML treated with subablative doses of chemotherapy without autotransplant, autologous GVHD can be induced, although at an incidence lower than that reported for CsA-induced GVHD following marrow transplantation. An enhancement of T cell and NK cell activity levels similar to experiences in syngeneic models of autologous GVHD was seen, but no direct autologous leukemic cell cytotoxicity could be demonstrated.

Adenovirus and retrovirus mediated interferon alpha gene transfer into CD34+ cells maintains regeneration capacity and enhances adhesion molecules in K562 cells.

BACKGROUND: Systemic administration of interferon-alpha (IFN-alpha) results in cytogenetic remissions and enhanced survival in a significant percentage of patients with chronic mylogenous leukemia (CML) and lymphoma. However, this treatment is associated with deleterious toxic effects. Gene transfer of the IFN-alpha gene into hematopoietic progenitors represents a novel strategy to deliver high concentrations of IFN-alpha to a local area. METHODS: We compared the effect of the transfer of the IFN-alpha gene on the cell growth and differentiation of several CD34+ cells in culture and in a NOD/SCID animal model, using adenovirus and retrovirus constructs. RESULTS: Transient local expression of the IFN-alpha gene using an adenovirus vector was associated with normal proliferation of CD34+ progenitors as measured by a colony forming unit of granulocyte-macrophage (CFU-GM) growth. Flow cytometric determination revealed that there was no significant difference in viability of these cells for 24-hour transduction periods. Reverse transcriptase/polymerase chain reaction (RT-PCR) analysis of RNA from CD34+ harvested CFU-GM progenitors demonstrated expression of IFN-alpha mRNA; radioimmunoassay (RIA) revealed that transduced cells secreted substantial levels of IFN-alpha protein. Furthermore, we constructed a retroviral vector in which IFN-alpha cDNA was driven by a viral LTR promoter to evaluate the effect of permanent IFN-alpha gene expression on cell growth. Retroviral packaging cells PA317 with high titers of retrovirus were produced and used to infect CD34+ and K562 cells. RIA showed that IFN-alpha-transduced CD34+ cells (with the aid of fibronectin fragment CH-296) produced approximately 400 units of IFN-alpha protein compared to CD34+ cells, or cells transduced with empty vector. IFN-alpha transduced CD34+ generated similar numbers of CFU-GM colonies as compared to control CD34+ cells. Engraftment of CD34+ cells transduced with IFN-alpha gene in NOD/SCID mice was successful for the first 30 days. Additionally, we studied the effect of local IFN-alpha expression on the cellular adhesion molecules, VLA-4, Mac-1, ICAM-1, and L-selectin in K562 cells, and human umbilical endothelial vein cells. K562 cells transduced with the IFN-alpha gene expressed a significantly elevated level of VLA-4, Mac-1, and ICAM-1. CONCLUSIONS: We conclude that expression of the IFN-alpha gene using retrovirus vectors results in an adequate localized expression of IFN-alpha mRNA and protein.

Human CD34+ hematopoietic cells transduced by retrovirus-mediated interferon alpha gene maintains regeneration capacity and engraftment in NOD/SCID mice.

To achieve long-term expression of human interferon alpha-5 (IFNalpha) gene in the bone marrow (BM) hematopoietic microenvironment, replication-deficient retroviral vector LSN-IFNalpha was used to deliver the IFNalpha gene into human BM CD34+ cells. After fibronectin-facilitated transduction, a fraction of CD34+ cells was plated in methylcellulose medium with or without G418 to assess transduction efficiency and the effect of IFNalpha gene transfer on colony formation. Colony-forming assay in the presence of G418 (400 microg/mL) revealed that 41% CFU-GM colonies are G418 resistant after infection with LSN-IFNalpha retrovirus. There was no significant difference in CFU-GM/BFU-E colony formation among IFNalpha gene-transduced CD34+ cells, control vector (LXSN) transduced-CD34+ cells and nontransduced CD34+ cells. Another portion of CD34+ cells was grown in liquid medium to measure IFNalpha production. RIA revealed that IFNalpha gene-transduced CD34+ cells produced 72.2 +/- 15.4 U/mL (10(6) cells/24 hours) of IFNalpha compared with 8.3 +/- 2.1 U/mL and 4.3 +/- 1.2 U/mL in LXSN-transduced or nontransduced CD34+ cells, respectively. The remaining portion of transduced CD34+ cells was transplanted into immunodeficient (NOD/SCID) mice to allow analysis of long-term expression of IFNalpha. Transplantation of 1x10(6) CD34+ cells into sublethally irradiated NOD/SCID mice showed that IFNalpha and neo(r) mRNA were detectable in engrafted mouse BM cells for up to 6 months. We conclude that continual local expression of IFNalpha in transduced CD34+ cells does not impair either CD34+ cell growth and differentiation or engraftment and long-term survival in NOD/SCID mice.

Regulation of growth and apoptosis of breast cancer cells by a 54 kDa lymphokine.

A normal human lymphocyte-derived 54 kDa polypeptide, capable of regulating cell growth has been identified as an isoform variant (abbreviated as NP54) of protein neuroleukin-phosphoglucose isomerase (PGI). Since distinct PGI variants undetectable in normal tissues had been identified in breast cancer tissues, the effect of NP54 on the growth of human breast cancer cells SK-Br-3 in cultures was analyzed. Exposure to NP54 caused a dose-dependent growth modulation. Approximately 40% reduction of cell density was detected at 40 pM of NP54, along with a blocking of G1 cells entering into S phase. The growth modulation was correlated with a significantly reduced expression of epidermal growth factor receptor (EGF-R) gene transcript, supporting the interpretation that the level of EGF-R expression and cell growth are related mechanisms. NP54 treatment also significantly increased cells with apoptotic morphological feature and fragmented DNA. Incubation with a monoclonal anti-NP54 antibody negated NP54 activity, confirming a regulatory activity in cell growth and apoptosis.

Colonic adenomas with extramedullary myeloid tumor (granulocytic sarcoma).

Extramedullary myeloid tumor (EMT) is an accumulation of malignant immature cells of the granulocytic series that is usually green in appearance due to the presence of myeloperoxidase. These invasive and destructive tumors occur most commonly in the skull and surrounding tissues, lymph nodes, skin and soft tissues. Regardless of the site, EMTs are difficult to recognize and may be easily overlooked or diagnosed as malignant lymphoma. EMTs may precede the diagnosis of a chronic myeloproliferative disorder or acute myeloid leukemia, may present coincident with the hematologic diagnosis, or may herald a relapse after therapy. An accurate diagnosis of EMT is of great clinical importance in the ongoing management of hematologic malignancies. We report here two unusual cases of EMT of the colon, which infiltrated adenomatous polyps. We conclude that increased cellularity within the lamina propria of polyps and mucosal surfaces in general should be carefully examined.