Sirolimus Combined with Dexamethasone for the Treatment of a Patient with Interferon Resistant Hydroa Vacciniform-Like Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4992-4992
Author(s):  
Zhigang Liu ◽  
Yongqian Jia ◽  
Yuping Gong ◽  
Yong Guo ◽  
Jiazhuo Liu ◽  
...  
Keyword(s):  
T Cell ◽  
Conflicts Of Interest ◽  
Serum Biochemistry ◽  
Skin Lesions ◽  
Cytotoxic T Cell ◽  
Cell Phenotype ◽  
Ebv Dna ◽  
One Year

Abstract Abstract 4992 Hydroa vacciniform-like lymphoma is an unusual pediatric cutaneous T-cell lymphoma, which rarely involved with adults. Chemotherapy and/or radiotherapy had little or no benefit. Patients may have a response to α-interferon. We report here an adult case with interferon resistant hydroa vacciniform-like lymphoma that has been successfully treated with sirolimus, an mTOR pathway inhibitor. The patient is a thirty-five year old women,she begun with recurrent cutanous rash and small vesicule around her mouth and nose 3 years ago. One year before, the symptoms were exacerbated with obvious vesiculopapular eruption, edematous, blisters, ulcers, scarring and crusts in her face. Scattered vesiculopapular could be seen in her upper chest and extremities accompanied with fever and submandibular lymphadenopathy. Facial skin biopsy showed angiocentric infiltrates from the epidermis to the subjacent dermis. The infiltrate cells showed a cytotoxic T-cell phenotype, with positive TCR gene rearrangement and EBER expression in situ hybridization. EBV serum test showed EBV-IgA and IgG positive, but serum EBV-DNA was negative. Patient was given α-interferon 300 million units, intramuscularlly, two times a week, plus prednisone 30mg per day, orally. Patients' skin lesions were improved, but present recurrent episodes of papulovesicular eruptions. For the past 3 month patient had a recurrent high fever and exacerbated vesiculopapular eruptions and blisters. Laboratory test showed anemia and neutropenia, serum biochemistry and marrow examination confirmed that a lymphoma associated hematophagocytosis was complicated. Sirolimus was started at an initial dose of 1.5mg, orally, every 12 hours, combined with dexamethasone 10mg/day, intravenously. Three days later the fever begun to resolved and the skin lesion gradually subsided. Two weeks later the skin lesions disappeared and the dose of sirolinmus begun to tapered to 1.0mg, orally, every 12 hours, with prednisone 30mg/day, orally. By three month of follow-up the patient still on stable and be observed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CD30 (Ki-1)-positive malignant lymphomas: clinical, immunophenotypic, histologic, and genetic characteristics and differences with Hodgkin's disease

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2905-2917 ◽  
Author(s):  
DA Filippa ◽  
M Ladanyi ◽  
N Wollner ◽  
DJ Straus ◽  
JP O'Brien ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Bone Marrow Involvement ◽  
Skin Lesions ◽  
Cell Phenotype ◽  
Cell Type ◽  
Null Cell

This study compares the histologic and immunophenotypic features of 71 cases of primary CD30+ diffuse large-cell lymphomas (DLCL) and 128 cases of Hodgkin's disease (HD) and discusses the clinical features of 52 patients with CD30+ DLCL. It includes analysis of sites of involvement, staging, response to treatment, sites and treatment of recurrences, and disease-free and overall survival. Diagnostic immunophenotypic differences were found between CD30+ DLCL and HD. All cases of CD30+ DLCL were positive for one or more common or lineage- specific lymphocyte antigens or for EMA. In contrast, 96.9% of HD cases were negative for CD45, CD45-RO, CD43, and CD20. The four exceptions are discussed. All cases of HD were negative for EMA. In patients with CD30+ DLCL, a T-cell phenotype was found in 60%, a null-cell type in 22%, and a B-cell type in 18% of the cases. The median age of patients with T- and null-cell phenotype was 22 years (range, 4 to 72). Fifty- two percent of them had high-stage (III and IV) disease and 61% had extranodal involvement at presentation, including 25% with skin lesions. Lymph nodes draining the skin lesions became involved in seven of 11 patients. No patient had initial bone marrow involvement. Most patients were treated with chemotherapy, and 83% had a complete remission. Fifty-four percent remain free of disease with a median follow-up of 47 months. Thirteen patients (29%) had one or more recurrences and five of them remain free of disease after salvage therapy, with a median follow-up period of 79 months. The clinical stage did not affect survival, probably as a result of different therapy. The t(2;5) translocation was found in five of 15 patients who had cytogenetic abnormalities. Of the other 10 cases, the translocation was detected by reverse transcriptase-polymerase chain reaction (RT- PCR) in four of five cases studied. All nine cases were of T- or null- cell phenotype. The cases of B-cell CD30+ DLCL had a characteristic immunophenotype. All were negative for EMA. These patients were older and had frequent bone marrow involvement but no skin infiltration by lymphoma. All three patients who were human immunodeficiency virus- positive (HIV+) had lymphomas of B-cell lineage. Detection of the t(2;5) translocation by molecular genetics is a useful and highly specific marker in the differential diagnosis between HD and CD30+ DLCL.

Cutaneous lymphomas other than mycosis fungoides: follow-up study of 52 patients.

1991 ◽  
Vol 9 (11) ◽  
pp. 1994-2001 ◽  
Author(s):  
P Joly ◽  
F Charlotte ◽  
M Leibowitch ◽  
C Haioun ◽  
J Wechsler ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Mycosis Fungoides ◽  
Stage Iv ◽  
Disease Stage ◽  
Cell Phenotype ◽  
Low Grade ◽  
Cutaneous Lymphomas ◽  
Radiotherapy Alone

Cutaneous lymphomas other than mycosis fungoides (MF) represent a rare and heterogeneous group of lymphomas. Their clinical behavior remains largely unknown. In this study, the clinical and immunohistologic characteristics and follow-up data of 52 well-documented cases of cutaneous lymphomas other than MF, presenting with initial cutaneous lesions, were reviewed. Twenty-seven patients presented with skin disease alone (stage IE), and 25 patients had concurrent cutaneous and extracutaneous disease (stage IV). The tumors were grouped into high-grade lymphomas (HGLs; 21%), intermediate-grade lymphomas (IGLs; 58%), and low-grade lymphomas (LGLs; 21%). A B-cell phenotype was most often expressed by cutaneous lymphomas (73%), particularly by stage IE lymphomas (85%). Among 13 cases of T-cell lymphomas, loss of one of the pan-T-cell antigens was detected in all cases but one. The clinical course of cutaneous lymphoma was closely dependent on stage and histologic subtype but not on T-cell or B-cell phenotype. Of 20 patients with stage IV HGL or IGL, 13 were treated by polychemotherapy with curative potential. Their median survival was 37 months. Fourteen patients with stage IE HGL or IGL were treated by radiotherapy alone. Nine patients (69%) relapsed within 2 years posttreatment. Seven of them relapsed in the skin outside the initial site involved, suggesting that radiotherapy alone is not an adequate treatment for these patients. Preliminary results concerning seven other patients with stage IE IGL or HGL treated by an initial third-generation polychemotherapy regimen are presented.

Carpal Tunnel Syndrome Associated with Bifid Median Nerve and Palmaris Profundus - Case Report and Literature Review

2019 ◽  
Vol 24 (02) ◽  
pp. 238-242
Author(s):  
Francesco Kostoris ◽  
Stefania Bassini ◽  
Emiliano Longo ◽  
Luigi Murena
Keyword(s):  
Median Nerve ◽  
Carpal Tunnel ◽  
Rare Case ◽  
Direct Compression ◽  
Transverse Carpal Ligament ◽  
Accidental Injury ◽  
Tunnel Syndrome ◽  
One Year

The anatomic variations of the median nerve and of the muscles of the wrist have been widely reported in literature. It is essential for the surgeon to be familiar with these variations in order to avoid accidental injury to the nerve during surgery. We report a rare case of bifid median nerve accompanied by an anomalous tendon of palmaris profundus discovered during the surgical release of carpal tunnel. The transverse carpal ligament was dissected and the anomalous tendon was left in situ because any direct compression over the median nerve was noticed intraoperatively. The patient was evaluated one year postoperatively clinically and radiologically (with MRI). At the follow up the resolution of symptoms was complete and the sleep disturbance was solved. The patient achieved a postoperative QuickDASH score of 9.1 and a Michigan Hand Questionnaire outcome score of 90 points.

Malodorous Skin Lesions in a Diabetic Patient: Infectious Versus Neoplastic

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S113-S114
Author(s):  
Ismail Elbaz Younes ◽  
Julia Rewerska ◽  
Victoria Alagiozian-Angelova
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Clinical Information ◽  
Skin Lesions ◽  
T Cell Lymphoma ◽  
Cytotoxic T Cell ◽  
Lymphoid Tissues ◽  
Rare Entity ◽  
Lymphomatoid Papulosis ◽  
Type D

Abstract Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma is a rare entity accounting for <1% of all cutaneous T-cell lymphomas. Almost all patients present with generalized skin lesions. This type of lymphoma has an extremely aggressive course with a median survival of 12 months. It tends to spread to other visceral sites, but lymph nodes are usually spared. We describe a case of a 59-year-old male with multiple necrotic malodours ulcers for several months. The first lesion was on his left thigh, followed by another lesion on his right chest and right eyelid. Medical history revealed newly diagnosed diabetes mellitus. The patient received antibiotics, presumptively for infectious etiology of the skin lesion, with no improvement. The right thigh lesion was excised and histomorphologic examination revealed a deep dermal proliferation of large-sized pleomorphic cells with marked pagetoid epidermotropism and skin ulceration. The adnexal skin structures were invaded by the lesion. The lesional cells were immunoreactive for CD3, CD7, CD8, and granzyme B; they were negative for CD4, CD5, CD56, and CD30. The immunophenotype confirms the entity that we have at hand in addition to the similar clinical picture that the patient presented with. This disease usually shows clonal TR gene rearrangements; nonetheless, no specific mutational aberration has been described. Our patient received chemotherapy; however, new lesions continued to erupt and he opted to proceed with palliative care. Clinical information is needed to give this diagnosis as it may look identical to a variant of lymphomatoid papulosis (type D), CD8-positive cutaneous T-cell lymphoma. We present this case due to the importance of clinical pathologic coloration to prevent misdiagnosis with mimickers as the ones pointed out earlier, and it is a provisional rare entity in the 2018 WHO classification of Tumors of Haematopoietic and Lymphoid Tissues.

One-Year Follow-up of Corneal Confocal Microscopy After Corneal Cross-Linking in Patients With Post Laser In Situ Keratosmileusis Ectasia and Keratoconus

2009 ◽  
Vol 147 (5) ◽  
pp. 774-778.e1 ◽  
Author(s):  
George D. Kymionis ◽  
Vasilios F. Diakonis ◽  
Maria Kalyvianaki ◽  
Dimitra Portaliou ◽  
Charalampos Siganos ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Cross Linking ◽  
Corneal Confocal Microscopy ◽  
One Year

T Cell Depletion with Alemtuzumab Is Associated with a High Incidence of EBV Viraemia but Low Risk of PTLD Following Allogeneic Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1177-1177
Author(s):  
Ben Carpenter ◽  
Maria Dimopoulou ◽  
Nilusha Manji ◽  
Tanzina Haque ◽  
Claire Atkinson ◽  
...  
Keyword(s):  
T Cell ◽  
Post Transplantation ◽  
Allogeneic Hsct ◽  
Ebv Reactivation ◽  
Unrelated Donors ◽  
Ebv Dna ◽  
High Level

Abstract Re-activation of latent EBV infection is a significant risk following T-cell depleted (TCD) allogeneic HSCT. The clinical course can range from asymptomatic viraemia to the development of post-transplantation lymphoproliferative disease (PTLD) and death. Since alemtuzumab depletes both T and B cells, it has been proposed that the risk of PTLD will be reduced compared to other TCD protocols. In an attempt to determine the risk of EBV viraemia or PTLD following allogeneic HSCT employing alemtuzumab-containing conditioning protocols, we reviewed outcomes in 91 consecutive adult patients treated at our institution. Of these, 84 patients had &gt;6 months follow-up and are included in this analysis. Two strategies of TCD were employed in this cohort: in vivo TCD with alemtuzumab (median dose 100mg) as part of a reduced intensity regimen (fludarabine based n=51); and in vitro TCD of the PBSC graft with 20 mg alemtuzumab ‘in the bag’ following conventional myeloablative conditioning (n=33). We have shown previously that alemtuzumab antibody levels persist for longer periods (up to 8 weeks ) following this in vivo depletion strategy compared to the in vitro approach [Morris et al. Blood 2003 102:404–6]. The median follow-up is 337 days and median age was 43 years (range 16–67 years). Diagnoses were AML/MDS (n=39), NHL (n=16), Hodgkins lymphoma (n=11), MPD (n=7), CLL (n=5) and other (n=6). 41/84 had HLA-identical sibling donors, 2 mismatched sibling donors, 21 matched unrelated donors and 20 mismatched unrelated donors. Monitoring for EBV load was performed by TaqMan whole blood real time PCR on a weekly basis for 100 days post transplantation and then as seen for follow-up. Positive results defined as &gt;200 copies/ml of EBV DNA. All patients with high levels of EBV viraemia (EBV DNA level &gt; 40,000 copies/ml) underwent CT imaging, bone marrow examination and lumbar puncture followed by withdrawal of immunosuppression and a single infusion of 375mg/m2 Rituximab as per institution policy. Of 82 patients where serostatus was available, 92.7 % were anti-EBV IgG positive. The 12-month cumulative incidence (CI) of EBV reactivation was 34.5% (39.2% following in vivo TCD versus 27.3% following in vitro TCD, p=0.2). Median peak viral load was 1,922 copies/ml (range 205–6,210,000). The 12 month CI of high-level EBV viraemia (&gt;40,000 copies/ml) was 11.9% (7.84% following in vivo TCD versus 18.2% following in vitro TCD, p=0.19). Patients re-activated EBV at a median of 86 days post transplant (range 21–380 days). The median duration of viraemia was 42 days (range 1–460 days). The 12-month CI of recurrent EBV re-activation (&gt;1 episode) was 21.4% (15.5% following in vivo TCD versus 25.5% following in vitro TCD, p=0.4). Of 10 patients with high-level EBV viraemia, 1 patient had PTLD as confirmed by histology. 8 of 10 patients received a single dose of Rituximab and this was associated with a rapid decline in EBV DNA load to undetectable levels in all cases. No adverse events secondary to Rituximab were noted. The patient with PTLD was given a second dose of Rituximab and attained a CR that persists at 334 days post treatment. 12-month non-relapse mortality was 10% in patients who had EBV reactivation and 27.7% in patients without EBV reactivation (p=0.06). Baseline and post-transplantation characteristics of sex, age, diagnosis, in vivo vs. in vitro alemtuzumab, donor type, CMV viraemia and presence of past or active acute GVHD were not related to re-activation of EBV by uni- or multivariate analysis in this patient cohort. In summary, this report demonstrates that TCD using alemtuzumab-containing conditioning protocols is associated with a high frequency of EBV viraemia but low risk of PTLD or non-relapse death in a cohort of patients treated pre-emptively with Rituximab for high EBV DNA loads.

Effect of T-Cell Dose On Outcomes After Peripheral Blood Allogeneic Hematopoietic Cell Transplantation in Hematological Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1171-1171
Author(s):  
Abraham S Kanate ◽  
Farhad Khimani ◽  
Aaron Cumpston ◽  
Kathy Watkins ◽  
Sonia Leadmon ◽  
...  
Keyword(s):  
T Cell ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Acute Gvhd ◽  
Hematopoietic Cell ◽  
Cell Dose ◽  
All Cause Mortality ◽  
Cd8 Cell ◽  
One Year

Abstract Abstract 1171 Poster Board I-193 Purpose: Peripheral blood allogeneic hematopoietic cell transplant (HCT) is used to treat various types of hematological malignancies. Current knowledge supports that increased CD34 + cell dose in the infusate is associated with earlier leukocyte recovery. The dose of CD3 +, CD4 + and CD8 + cells is largely disregarded except in T-cell depleted transplant. The correlation between various cell doses and outcomes is an area of great interest in HCT. Our analysis focuses on the impact of T-cell subset dosing, on outcomes after HCT, such as acute graft versus host disease (GVHD) and mortality. Methods: Retrospective analysis was conducted on 134 consecutive patients who underwent peripheral blood allogeneic HCT for various hematological malignancies in our institution between January 2003 and December 2008. Statistical analysis was performed using SPSS 15.0. The Chi - square test was used to determine any association between cell doses and the incidence of acute GVHD and all-cause mortality at one year of follow-up after transplant. Results were also compared with the association between CD3+ and CD8+ cell doses and incidence of acute GVHD as reported in 2007 by our institution. Results: A total of 134 patients were included in our analysis, consisting of 49 females and 85 males. The median age was 49 years (range 17-69). HCT was from matched related donors in 68 and from matched unrelated donors in 66 patients. A variety of conditioning regimens were used in preparation for the HCT. Overall survival at 1 year of follow-up was 60%, the incidence of acute GVHD was 52%, and chronic GVHD was 29%. All-cause mortality at one year follow up was found to be significantly higher when the CD3+ cell dose was < 30.5 × 107/kg IBW (49% vs. 29%, P = 0.018). All-cause mortality was also significantly increased when CD8+ cell dose was < 9.2 × 107/kg IBW (50% vs. 33%, P= 0.05). A CD8+ cell dose of < 9.2 × 107/kg IBW was also associated with an increased risk of grades 2-4 acute GVHD (48% vs. 22%, P = 0.026). There was no association of statistical significance between CD3+ and CD4+ cell doses and the incidence of acute GVHD. Conclusion: The data suggests a statistically significant inverse association between mortality and CD3+ cell dose of <30.5 × 107/kg IBW. A CD8+ cell dose of <9.2 × 107/kg IBW was also associated with increased all-cause mortality and acute GVHD (grades 2-4). Our institution reported in 2007, a significant association between the incidence of acute GVHD (grades 2-4) and CD3+ cell dose < 33.5 × 107/kg IBW and CD8+ cell dose of < 6.2 × 107/kg IBW, based on series of 66 patients. As we increased the sample size to 134, the association between CD3+ cell dose and acute GVHD was no more present. We conclude that T-cell dose is an important factor in terms of outcomes after all allogeneic HCT irrespective of preparative regimen. T-cell subsets likely play a pivotal role in transplant results, though it is not well described. Analysis of larger databases is required to substantiate our results. Disclosures: No relevant conflicts of interest to declare.

IL-2 + Anti-IL2 Complex in Situ Stimulation of Host Tregs Combined with Absence of Donor B7.1 / B7.2: A Novel Approach to Facilitate Chimerism in RIC MHC-Matched Miha-Mismatched BMT Recipients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2441-2441
Author(s):  
Monica Jones ◽  
Alwi Shatry ◽  
Bruce R. Blazar ◽  
Robert B. Levy
Keyword(s):  
T Cell ◽  
Conflicts Of Interest ◽  
Donor Cell ◽  
Allogeneic Transplantation ◽  
Treg Cells ◽  
Hematopoietic Stem ◽  
Novel Approach ◽  
Successful Induction ◽  
Stimulation Of

Abstract Abstract 2441 Poster Board II-418 Reducing and ultimately eliminating conditioning while enabling donor cell engraftment remains an elusive goal of allogeneic hematopoietic stem cell transplantation. The control of host resistance (HVG) to donor allogeneic transplantation antigens is pivotal for engraftment and the successful induction and maintenance of immune tolerance. Using a well characterized minor histocompatibility antigen (MiHA) matched allogeneic (HSCT) model, we have demonstrated a requirement for CD80/CD86 expression on donor APC in order to elicit resistance under reduced intensity conditioning (RIC) of 5.5Gy TBI. Based on this observation, we hypothesize that expansion of host Treg cells which may engage donor APC – the site of host anti-donor Tconv activation - is an advantageous strategy to effectively inhibit HVG responses. To address this hypothesis, we reduced TBI almost 30% to 4.0Gy, and found that even recipients transplanted with 4×106 CD80-/-CD86-/- T cell depleted donor BMC failed to engraft. Experiments were therefore initiated to target and rapidly expand host Tregs by administering IL-2 + anti-IL2 (IAC) complex to further strengthen suppression of HVG. C3H.SW (H2b) recipient mice were conditioned with 4.0Gy TBI (D-1) and B6-CD80-/-CD86-/- TCD-BM (H2b, 7×106) infused on the following day (D0). IAC was introduced on the day of conditioning (D-1) and then daily on days D 0, 1 and 2. We reported that anti-IL-2 + IL-2 complex can expand residual host Treg cells in RIC recipients (Blood, 113:733-743, 2009; Biol. Blood Marrow Transplantation. 15: 785-794, 2009). One month later, 1/3 of mice receiving complex – but not untreated controls demonstrated significant levels (15% B220+) of hematopoietic chimerism. These results, while encouraging, indicated that stimulation of the endogenous Treg compartment alone in 4.0 Gy recipients was not sufficient to regulate the HVG response. We then modified our approach by infusing 1×106 recipient Tregs obtained from normal C3H.SW mice one day following 4.0Gy RIC, i.e. at D0 and began expanding these cells with IAC injected early on D0 and again on D1 prior to the B6-CD80-/-CD86-/- TCD-BM graft – delayed one day and administered on D1. 100% of these recipients (n=3/gr) exhibited high donor chimerism (43.7+/-10.8 SD) 6 weeks post-HSCT, whereas all non-Treg infused control recipients rejected these marrow allografts. Results of 4 independent transplant experiments demonstrated 10/12 recipients contained similar levels of B220+ chimerism (mean donor: 53.9%) and significant T cell chimerism (mean donor: CD4, 19.8%; CD8, 35%). When both host Tregs and IAC were employed, strong chimerism was observed using 4 or 7×106 CD80-/-86-/- TCD-BM grafts. Notably, addition of 1×106 donor (i.e. B6-wt) Tregs and IAC treatment did not augment chimerism vs. IAC only in 4.0Gy conditioned C3H.SW recipients. These results suggest that the introduction of host Tregs 2 days prior to the BM graft allowed adequate time for IAC to mediate Treg expansion in the lymphopenic environment to generate sufficient Treg levels and together with the absence of donor APC B7 signaling to host Tconv cells overcome, i.e. suppressed HVG responses. Transplants were then performed using the identical Treg and IAC protocol with B6-wt TCD-BM which is readily rejected in 4.0 Gy TBI conditioned recipients. Despite the presence of B71/2 on B6-wt donor APC, one-third of the recipients receiving an infusion of host Tregs and IAC treatment exhibited chimerism, although lower (6.3%) than observed with B7.1/2 deficient donors. Transplants of wild type TCD-BM into MiHA mismatched recipients will determine how anti-B7.1/2 mab blockade, together with rapid in situ expansion of infused host Tregs post-TBI and pre-HSCT can be utilized to further diminish immunosuppressive TBI conditioning (<4.0 Gy) regimens. Disclosures: No relevant conflicts of interest to declare.

Attempt to Discontinue Imatinib Following Interferon Alfa Pre-Treatment In Chronic Phase CML Patients Achieving Stable Complete Cytogentic Responses (CCyR)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4898-4898
Author(s):  
Izhar Hardan ◽  
Yulia Volchek ◽  
Tali Tohami ◽  
Ninette Amariglio ◽  
Luba Trakhtenbrot ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Chronic Phase ◽  
Interferon Alfa ◽  
Cytotoxic T Cell ◽  
Molecular Response ◽  
Molecular Remission ◽  
Line Therapy ◽  
Pre Treatment

Abstract Abstract 4898 Imatinib (IM) has been shown to induce sustained clinical responses and stable remissions resulting in improved survival in chronic phase (CP) CML patients (pts.). Currently the state of the art is life long continuation of IM therapy which raises issues like the emergence of drug resistance, long-term safety and tolerability, compliance and costs. Interferon Alfa (IFNα), which has anti-CML activity and may induce major cytogenetic responses (MCyR), has in contrast to IM, immunoregulatory properties including the induction of anti-CML cytotoxic T-cell activity. Moreover, in initial studies of IM discontinuation it seemed that previous IFNα exposure was beneficial for the maintenance of molecular remission after IM cessation. We, therefore, hypothesized that adding IFNα to IM prior to IM discontinuation will increase the proportion of pts. remaining in continuous molecular response. We report on the long term, median follow up of 40 months (range, 33–41), outcome of CP CML pts. who discontinued IM after the addition of IFNα. CP CML pts. in CCyR for ≥2 years on IM were included. Study pts. received a combination of PegIFN (Pegasys, Roche) (180 μg/week, sc) and IM (400 mg) for 9 months followed by 3 months of PegIFN monotherapy, and were followed up thereafter without any anti leukemia therapy. Twelve CP CML pts. were included, 9 males and 3 females. Median age was 50.5 years (range, 33–67). Disease duration was 67 (18-96) months. Eight of the pts. (67%) received IFNα prior to IM as first line therapy. Eight of the patients had a major molecular response (MMR), 2 were in complete molecular response (CMR) (of 48 and 10 months duration) and 2 had less than a MMR. Of the evaluable pts. only 1 had a BCR ABL KD mutation (E373D). IFNα dose had to be reduce to 90–135 μg/week, sc due to intolerance in 10/12 pts. Median duration of CCyR (n=12) and MMR (n=8) at the time of IM discontinuation was 47.5 (21-86) months and 19.5 (9-84) months, respectively. Cytogenetic relapse occurred in 8 pts. 8 (2-38) months after IM discontinuation. Loss of molecular responses could be detected in all 8 pts. during follow up, and prior to the cytogenetic relapse at 8 (1-25) months post IM discontinuation. An additional 1 pt. had a molecular relapse but has maintained his CCyR 20 months post IM discontinuation. IM (400 mg/day) was reintroduced in all 8 pts. with loss of CCyR and they all re-achieved a CCyR 3.5 (3-7) months after IM re initiation. Five of the 8 pts. (62%) achieved also a MMR at 5, 7, 8, 10, and 11 months post IM re- administration, respectively. After a median follow up of 40 (range 33–41) months, 4 of the 12 study pts. (33.3%) are in persistent molecular remission. These 4 pts. achieved a CMR (n=1) (of 10 months duration) or MMR (n=3) (of 8, 14 and 19 months, respectively) prior to IM discontinuation. Notably, 2 of these 4 pts. had IFNα exposure as front line therapy pre-IM initiation. In summary, only a minority of CML pts. with stable MMR or CMR have a long lasting remission and will not relapse following IM discontinuation. Pts. having a cytogenetic relapse after IM discontinuation respond to IM re-administration by re-achieving CCyR and mostly MMR. The role of IFNα pre treatment, as well as the depth of molecular response needed to be achieved pre-IM discontinuation, should be further evaluated in a well designed 2 arms controlled randomized studies. Disclosures: No relevant conflicts of interest to declare.

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