Cancer Treatment Today » Burkitt’s and Aggressive Lymphomas

Angioimmunoblastic T-cell – pro

M Levin, MD — Tue, 04 Sep 2012 15:13:14 +0000

Angioimmunoblastic T-cell lymphoma (AILD) is considered a variety of T-cell lymphoma, which usually occurs in adults. Patients present with profound lymphadenopathy, fever, night sweats, weight loss, skin rash, a positive Coomb’s test, and polyclonal hypergammaglobulinemia. It is quite rare and no standrd approach has beend efined. Angioimmunoblastic T-cell lymphoma was formerly called angioimmunoblastic lymphadenopathy with dysproteinemia. Characterized by clonal T-cell receptor gene rearrangement, this entity is managed like diffuse large cell lymphoma. Opportunistic infections are frequent due to an underlying immune deficiency. Doxorubicin-based combination chemotherapy is recommended as it is for other aggressive lymphomas. Myeloablative chemotherapy and radiation therapy with autologous peripheral stem cell support has been described in anecdotal reports. Occasional spontaneous remissions and protracted responses to steroids only have been reported. A few patients may progress to an EBV-positive diffuse large B-cell lymphoma. I have not found any studies reporting the use of autologous SC for this entity. A recent (2006) retrospective review of ASCT in T-cell lymhomas reported good results in 6 angioimmunoblastic lymphoma patients. All angioimmunoblastic T-cell lymphoma (AILT) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients achieved CR; 5 of 6 have remained disease free for more than 3 years. However, this is a very small sample.

A search of current trials reveals a variety of investigtional approaches to this disease, including stem cell transplant in second remission.

http://clinicaltrials.gov/ct/search?term=%22T-cell+lymphoma%22+%5BCONDITION%5D+AND+angioimmunoblastic+%5BALL-FIELDS%5D&submit=Search

Reimer P, Schertlin T, Rüdiger T, et al.: Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study. Hematol J 5 (4): 304-11, 2004.

Pautier P, Devidas A, Delmer A et al. Angioimmunoblastic-like T-cell non Hodgkin’s lymphoma: outcome after chemotherapy in 33 patients and review of the literature. Leuk Lymphoma 1999; 32: 545–552

Yamazaki T, Sawada U, Kura Y, et al.
Treatment of high-risk peripheral T-Cell lymphomas other than anaplastic large-cell lymphoma with a dose-intensified CHOP regimen followed by high-dose chemotherapy
ACTA HAEMATOLOGICA 116 (2): 90-95 2006

T Cell Lymphoma – pro

M Levin, MD — Sun, 02 Sep 2012 16:38:39 +0000

Lay Summary: Not much is known about NK1 T lymphomas. This post briefly describes what is known.

This kind of lymphoma tend to be indolent but not all that much is known about hatural history of these neoplasms and some patients do poorly. Patients with natural killer T (NK/T) -cell lymphomas have poor survival outcome, and for this condition there is no optimal therapy. A recent review found that following treatments tend to be used: Patients received one of the following initial treatment modalities: (1) an anthracycline-containing chemotherapeutic regimen followed by radiotherapy (RT); (2) a non–anthracycline-containing chemotherapeutic regimen followed by RT; (3) anthracycline-based chemotherapy; (4) non–anthracycline-based chemotherapy; (5) involved-field RT as the primary treatment; (6) surgery alone; and (7) supportive care only. The anthracycline-based regimens used were as following: cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP); dose-escalated CHOP (deCHOP); cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin, procarbazine (COPBLAM); and (etoposide, doxorubicin, vincristine, cyclophosphamide, prednisolone (EPOCH). The non–anthracycline-containing regimens used were ifosfamide, methotrexate, etoposide (IMEP); dexamethasone, ifosfamide, cisplatin, etoposide (DICE); etoposide, methylprednisolone, cisplatin, cytarabine (ESHAP); dexamethasone, cytarabine, cisplatin (DHAP); etoposide, ifosfamide, cisplatin, dexamethasone (VIPD); and cyclophosphamide, vincristine, prednisone (CVP). In patients with localized disease, involved-field radiotherapy was given at the physician’s discretion following chemotherapy. The treatment response was assessed according to standard response criteria.
An ongoing study of EPOCH/CaMPATH is referenced below. The proposed study is described briefly as follows: “This study will examine the safety and effectiveness of combination therapy with the monoclonal antibody Campath-1H and continuous infusion of a chemotherapy regimen called EPOCH for treating non-Hodgkin’s T-cell and NK-cell lymphomas. In general, T-cell and NK-cell lymphomas are less responsive to standard treatments than B-cell lymphomas. EPOCH, which includes the drugs doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone, has shown a high degree of effectiveness in patients whose tumors have stopped responding to standard regimens. Campath-1H may improve the effects of chemotherapy.”

Stem Cell transplantation is in the infant stages for this disease.

http://clinicalstudies.info.nih.gov/detail/A_2003-C-0304.html

Jeeyun Lee, Cheolwon Suh, Yeon Hee Park, Young H. Ko, Soo Mee Bang, Jae Hoon Lee, Dae Ho Lee, Jooryung Huh, Sung Yong Oh, Hyuk-Chan Kwon, Hyo Jin Kim, Soon Il Lee, Jung Han Kim, Jinny Park, Seok Joong Oh, Kihyun Kim, Chulwon Jung, Keunchil Park, Won Seog Kim
Extranodal Natural Killer T-Cell Lymphoma, Nasal-Type: A Prognostic Model From a Retrospective Multicenter Study Journal of Clinical Oncology, Vol 24, No 4 (February 1), 2006: pp. 612-618

Au WY, Lie AKW, Liang R, et al: Autologous stem cell transplantation for nasal NK/T-cell lymphoma: A progress report on its value. Ann Oncol 14:1673-1679, 2003

L. Pagano, A. Gallamini, G. Trape, L. Fianchi, D. Mattei, G. Todeschini, A. Spadea, S. Cinieri, E. Iannitto, M. Martelli, A. Nosari, E. D. Bona, M. E. Tosti, M. C. Petti, P. Falcucci, M. Montanaro, A. Pulsoni, L. M. Larocca, G. Leone, and For the Intergruppo Italiano Linfomi NK/T-cell lymphomas ‘nasal type’: an Italian multicentric retrospective survey Ann. Onc., May 1, 2006; 17(5): 794 – 800.

Autologous stem cell transplantation for non-Hodgkin’s lymphoma – pro

M Levin, MD — Sun, 02 Sep 2012 16:35:01 +0000

Lay Summary: Autologous stem cell transplantation is standard for relapsed non-Hodgkin’s lymphoma.

Patients with aggressive and intermediate non-Hodgkin’s lymphoma (NHL) treated at first diagnosis with polychemotherapy alone or combined chemoradiotherapy can achieve high response rates . However, patients with relapsed or progressive disease still have a poor prognosis. High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is the treatment of choice for these patients. The most compelling evidence for the superiority of HDCT compared with conventional-dose salvage therapy in relapsed and progressive NHL is based on the randomized ‘Parma trial. In this study, all patients received two cycles of conventional chemotherapy. The responders were randomized to receive either four cycles of conventional chemotherapy or HDCT (BEAM) followed by autologous stem cell transplantation (ASCT). The response rate was 44% in the group with conventional chemotherapy and 84% in the HDCT group. The analysis at 5 years revealed that patients treated with HDCT had superior outcome as measured by freedom from second failure (FF2F) (12% versus 46%) and by overall survival (OS, 32% and 53%). Therefore, two cycles of conventional salvage chemotherapy followed by HDCT and PBSCT is considered standard treatment for these patients. However, in the ‘Parma trial’ more than 50% of patients treated in the HDCT-arm relapsed and most of them died. New approached to improve these results are ongling; however, autologous stem cell transplantation for relapsed non-Hodgkin’s lymphoma is currently standard and NCCN recommended. On p. BCEL-6, NCCN recommends allogeneic transplant in selected cases, which it defiens as mobilization failure or persistent bone marrow involvement. The strategy of combining autologous and subsequent allogeneic transplant is experimental.

A. Josting et al, High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin’s lymphoma: results of a multicenter phase II study Annals of Oncology 2005 16(8):1359-1365

H. Tilly1 et al, Diffuse large B-cell non-Hodgkin’s lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Ann Oncol (2010) 21 (suppl 5): v172-v174.

American Society for Blood and Marrow Transplantation. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of diffuse large B cell lymphoma: update of the 2001 evidence-based review. Biol Blood Marrow Transplant 2011 Jan;17(1):18-9.

nccn.org, 2012

Revised July 10, 2011

ASCT for Burkitt’s – pro

M Levin, MD — Fri, 24 Aug 2012 01:41:52 +0000

Standard doxorubicin-based combination chemotherapy, such as CHOP, frequently induces remissions of short duration. In an attempt to obtain durable remissions, high-dose therapy (HDT) with autologous stem-cell support was given in a few centers for patients who were in remission upon CHOP-like induction therapy. In the last decade, several pediatric groups have obtained impressive results for BL- and B-cell acute lymphoblastic leukaemia patients by giving blocks of intensified chemotherapy for five to seven consecutive days with 2- to 3-week interval. Five-year disease-free and overall survival >90% in paediatric patients have been reported. In the German Adult Acute Lymphoblastic Leukaemia (ALL) 05/93 protocol, the BFM-90 protocol was adjusted with dose modifications for adult patients.

There was only one randomized study to my knowledge in aggressive lymphomas that compared standard chemotherapy and ASCT after remission. The long-term outcome for patients with aggressive non-Hodgkin’s lymphoma (NHL) is poor. Consequently, the European Organization for Research and Treatment of Cancer Lymphoma Group designed a prospective randomized trial to investigate whether high-dose chemotherapy plus autologous bone marrow transplantation (ABMT) after standard combination chemotherapy improves long-term survival. Patients aged 15–65 years with aggressive NHL received three cycles of CHVmP/BV polychemotherapy (i.e., a combination of cyclophosphamide, doxorubicin, teniposide, and prednisone, with bleomycin and vincristine added at mid-cycle). After these three cycles, patients with a complete or partial remission and at that time no lymphoma involvement in the bone marrow were randomly assigned to the ABMT arm (a further three cycles of CHVmP/BV followed by BEAC [i.e., a combination of carmustine, etoposide, cytarabine, and cyclophosphamide] chemotherapy and ABMT) or to the control arm (five more cycles of CHVmP/BV). From December 1990 through October 1998, 311 patients (median age = 44 years) were registered and received the first three cycles of CHVmP/BV, and 194 patients were randomly assigned to the treatment arms. Approximately 70% (140 patients) of these patients were of low or low–intermediate International Prognostic Index (IPI) risk. After a median follow-up of 53 months, an intention-to-treat analysis showed a time to disease progression and overall survival at 5 years of 61% (95% confidence interval [CI] = 51% to 72%) and 68% (95% CI = 57% to 79%), respectively, for the ABMT arm and 56% (95% CI = 45% to 67%) and 77% (95% CI = 67% to 86%), respectively, for the control arm. Differences between arms were not statistically significant. A subset analysis on IPI risk groups, although too small for reliable statistical analysis, yielded similar results. They concluded that”standard combination therapies remain the best choice for most patients with aggressive NHL. We recommend that patients with IPI low or low–intermediate risk not be subjected to high-dose chemotherapy and ABMT as a first-line therapy.”

Since 2000, a number of studies suggested efficacy of ASCT in HIV-related relapsed lymphoma. This includes a French study that reported OS and PFS rates of 30 and 20%, respectively, 3-years post-transplant in 14 HIV-related lymphomas. The largest study to date, involving 68 HIV-related lymphomas, reported that PFS was 56% at a median follow up of 32 months. CR and chemosensitive disease at ASCT were identified as the main favorable prognostic factors for survival, whilst the use of more than two pre-ASCT treatment lines, and failure to achieve CR at transplantation were found at multivariate analysis to be adverse prognostic factors for relapse. On relapse,2017 NCCN recommends a clinical trial, suppotive care or retreatment with high dose chemotherapy and stem cell transplant in selected patients. NCCN recommends transplantation, for relapse. It refers one from the AIDS Associate Lymphoma page to BCEL-6, where that treatment is listed.

Recent results from a multicenter, phase 2 trial suggest that patients with HIV and aggressive lymphoma should receive autologous stem cell transplant as standard of care. Risk of serious complications after undergoing autologous stem cell transplant in these patients is equal to that of patients who are not HIV infected Recent results from a multicenter, phase 2 trial suggest that patients with HIV and aggressive lymphoma should receive autologous stem cell transplant as standard of care. Risk of serious complications after undergoing autologous stem cell transplant in these patients is equal to that of patients who are not HIV infected

Alvarnas JC, Le Rademacher J, Wang Y, et al. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the (BMT CTN) 0803/(AMC) 071 Trial [published online June 13, 2016]. Blood. doi:10.1182/blood-2015-08-664706.

Betticher, D., Martinelli, G, Radford, J., Kaufmann, M, Dyer, M., Kaiser, U, Aulitzky, W., Beck, J, von Rohr, A, Kovascovics, T, Cogliatti, S., Cina, S, Maibach, R, Cerny, T, Linch, D. (2006). Sequential high dose chemotherapy as initial treatment for aggressive sub-types of Non-Hodgkin Lymphoma: results of the international randomized phase III trial (MISTRAL). Ann Oncol 17: 1546-1552

Stewart, D. A., Bahlis, N., Valentine, K., Balogh, A., Savoie, L., Morris, D. G., Jones, A., Brown, C., Russell, J. A. (2006). Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma. Blood 107: 4623-4627

A. Krishnan, A. Molina, J. Zaia, D. Smith, D. Vasquez, N. Kogut, P. M. Falk, J. Rosenthal, J. Alvarnas, and S. J. Forman
Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas
Blood, January 15, 2005; 105(2): 874 – 878.

Gabarre J, Marcelin AG, Azar N et al.: High-dose therapy plus autologous hematopoietic stem cell transplantation for human immunodeficiency virus (HIV)-related lymphoma: results and impact on HIV disease. Haematologica 89, 1100–1108 (2004).

Krishnan A, Molina A, Zaia J et al.: Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas. Blood 105, 874–878 (2005).

Balsalobre P, Diez-Martin JL, Re A et al.: Autologous stem-cell transplantation in patients with HIV-related lymphoma. J. Clin. Oncol. 27, 2192–2198 (2009).

Imrie K, Rumble RB, Crump M, Advisory Panel on Bone Marrow and Stem Cell Transplantation, Hematology Disease Site Group. Stem cell transplantation in adults: recommendations. Toronto (ON): Cancer Care Ontario Program in Evidence-based Care; 2009 Jan 30. 78 p. (Recommendation report; no. 1). [66 references]

Revised 3/11/2010

Umbilical cord stem cells – pro

M Levin, MD — Fri, 24 Aug 2012 01:39:37 +0000

Lay summary: Cord stem cells have been shown to be equivalent to other allogeneic cells for transplantation in leukemia but not yet for other diagnoses.

Cord blood transplantation is a fairly recent but rapidly becoming established technique for transplnatation in leukemia. The first unrelated cord blood transplantations were performed in children. The first 25 unrelated cord blood transplantations were reported in 1996. Since then a number of reports appeared. This work has been followed by several studies, showing similar results in children. The New York Blood Center reported on 562 cases, 82% children, who underwent transplantation in a variety of centers with differing conditioning regimens and graft-versus-host disease prophylaxis. However, there have been retrospective matched pair analyses. Two studies in the New England Journal of Medicine reinforce the role of cord-blood transplantation in the treatment of leukemia in adults. Although this treatment is not recommended over HLA-matched donors from unrelated donor sources, it is a viable alternative that can be effective. (N Engl J Med. 2004;351:2255-2265, 2276, 2328). Although guidelines have not yet listed this alternative, more recent review articles and an editorial state that it is an equivalently effective approach, even in adults. Both reports reinforce the role of cord-blood transplantation in the treatment of adults with leukemia. It is realistic to anticipate that the current results for cord-blood transplantation in adults with hematologic cancers will contribute to more extended use in the coming years.

There is an ongoing trial: Single or Double Umbilical Cord Blood Unit Transplantation Followed by GVHD Prophylaxis With FK506 and MMF, NCT00244036.

J. Aschan Allogeneic haematopoietic stem cell transplantation: current status and future outlook Br. Med. Bull., October 5, 2006; (2006)

Karen K. Ballen New trends in umbilical cord blood transplantation
Blood, 15 May 2005, Vol. 105, No. 10, pp. 3786-3792

Vikram Mathews, MD and John F. DiPersio, MD, PhD Stem Cell Transplantation in Acute Myelogenous Leukemia in First Remission: What Are the Options? Current Hematology Reports 2004,

Vikas Gupta1, Martin S. Tallman2, and Daniel J. Weisdorf, Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns. Blood: 117 (8); February 24, 2011

Salvage regimens for non- Hodgkin’s lymphoma – pro

M Levin, MD — Fri, 24 Aug 2012 01:38:07 +0000

Lay Summary: I discuss salvage regimens for aggressive of intermediate relapsed or refractory lymphoma.

Aggressive non-Hodgkin’s lymphoma is difficult to handle once it relapses or becomes refractory to chemotherapy. Various second or third line chemotherapies, which are called salvage chemotherapy, were developed without promising results. Improvement in efficacy by adding relatively new agent, rituximab, to chemotherapy is now widely accepted in non-Hodgkin’s lymphoma.

The consensus is that people with relapsed disease should be treated with salvage chemotherapy. The first systematic review identified 22 phase II studies (1210 people overall; individual trials from 20–208 people) using 15 different combinations of cytotoxic drugs for conventional dose second line (salvage) chemotherapy. The most common included drugs were etoposide (20 studies), ifosfamide (14 studies), and methotrexate (11 studies). Other drugs included cisplatin (6 studies), cytarabine (4 studies), mitoxantrone (3 studies), bleomycin (3 studies), and mitoguazone (3 studies). All 22 studies revealed similar results, with second line combination chemotherapy frequently inducing remission in people with relapsed or refractory aggressive non-Hodgkin’s lymphoma. The second review also reported the use of rituximab in non-controlled trials (number of trials not reported). The reviews found that overall 60–70% of people with relapsed disease showed objective tumour responses. Complete remission was seen in 20–40% of people. However, these remissions were frequently short lived, with a maximum of 10% of responders remaining disease free after 3–5 years. The authors of the reviews were unable to conclude that any particular salvage chemotherapy regimen was superior to any of the others from the literature reviewed.

There are no randomized controlled trials comparing different conventional dose salvage chemotherapy regimens (PACEBOM, ESHAP, RICE, IVAC) in people with relapsed aggressive non-Hodgkin’s lymphoma. The consensus is that people with relapsed disease should be treated with salvage chemotherapy. One systematic review identified 22 phase II trials of various conventional dose salvage chemotherapy regimens. All regimens reported similar response rates and no single superior regimen can be identified. There are likewise no studies confirming or disproving the additive effect of Rituximab but it is a well reported regimen and no clinical trials are currently investigatong RICE vs ICE chemotherapy.However, it is not proven. A clinical trial (NCT00367497) of R-ESHAP is currently recruiting patients.

MEHMET AKIF ÖZTÜRK et al, Modified ESHAP as salvage chemotherapy for recurrent or refractory non-Hodgkin’s lymphoma: Results of a single-center study of 32 patients Chemotherapy (Chemotherapy) 2002, vol. 48, no5, pp. 252-258

BMJ – Clinical Evidence – http://clinicalevidence.bmj.com/ceweb/conditions/bly/2401/2401_I5.jsp

Kimby E, Brandt L, Nygren P, et al. A systematic review of chemotherapy effects in aggressive non-Hodgkin’s lymphoma. Acta Oncol 2001;40:198–212.

Barosi G, Carella A, Lazzarino M, et al. Management of nodal diffuse large B-cell lymphomas: practice guidelines from the Italian Society of Haematology, the Italian Society of Experimental Haematology and the Italian Group for Bone Marrow Transplantation. Haematologica 2006;91:96–103.

Jerkeman M, Leppä S, Kvaløy S, Holte H.ICE (ifosfamide, carboplatin, etoposide) as second-line chemotherapy in relapsed or primary progressive aggressive lymphoma–the Nordic Lymphoma Group experience.Eur J Haematol. 2004 Sep;73(3):179-82.

DifH. Tilly, M. Dreyling, and On behalf of the ESMO Guidelines Working Group Diffuse large B-cell non-Hodgkin’s lymphoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up Ann Oncol (2010) 21 (suppl 5): v172-v174.

PET to”fish” for a diagnosis – pro

M Levin, MD — Fri, 24 Aug 2012 01:34:29 +0000

Lay Summary: PET should not be used to “fish” for a diagnosis. On the other hand, when a pathological diagnosis is already established, PET can be useful for follow-up, staging and reassessment after therapy.
PET scanning is an excellent modality to assess tumor size and metabolic activity and it is coming into wider use as supporting data becomes available for various tumor types. It can be used to distinguish benign and malignant tissues once a diagnosis has been made. Unfortunately, there is no literature to support use of PET to “fish” for diagnosis when no histologic diagnosis has been obtained. This is especially true of lymphadenopathy. Since lymphadenopathy can be caused by a variety of conditions with different degree of gadolinium uptake and different specificities, sensitivities and accuracies, PET is potentially misleading and even harmful when used in this fashion. A NCT00068146 study is looking at a related question: the usefulness of FDG-PET scanning in distinguishing autoimmune lymphoproliferative syndrome (ALPS) from lymphoma. Much more investigation will need to be done before PET can be used to distinguish different types of lymphadenopathies. While the use of PET is reasonable in some cancers when there is already a pathological diagnosis to distinguish benign from malignant disease sites or to evaluate a potential recurrence, it should not be used for this purpose before the diagnosis of malignancy had been established.

Woolley, Steven M, Rajesh, Pala Babu The Use of PET and PET/CT Scanning in Lung Cancer Asian Cardiovasc Thorac Ann 2008 16: 353-354

Cook GJR, Fogelman I, Maisey MN. Normal physiological and benign pathological variants of 18-FDG PET scanning: potential for error in interpretation. Sem Nucl Med 1996;26:308–14

S. Spiro, J. Buscombe, G. Cook, T. Eisen, F. Gleeson, M. O’Brien, M. Peake, N. Rowell, R. Seymour Ensuring the right PET scan for the right patient Lung Cancer, Volume 59, Issue 1, Pages 48-56, 2008

Ma, Yanru MD; Li, Fang MD; Chen, Libo MD, PhD, Widespread Hypermetabolic Lesions Due to Multicentric Form of Castleman Disease as the Cause of Fever of Unknown Origin Revealed by FDG PET/CT. Clinical Nuclear Medicine: October 2013 – Volume 38 – Issue 10 – p 835–837

Rossotti R, Moioli C, Schiantarelli C, et al. FDG-PET imaging in the diagnosis of HIV-associated multicentric Castleman disease: Something is still missing. Top Antivir Med. 2012;20(3):116-118.

Jamar F, Buscombe J, Chiti A, et al. EANM/SNMMI guideline for 18F-FDG use in inflammation and infection. J Nucl Med. 2013;54(4):647-658.

Bower M, Palfreeman A. Alfa-Wali M, et al. British HIV Association guidelines for HIV-associated malignancies 2014. HIV Medicine. 2014;15 (Suppl. 2): 1-92.

Donor Lymphocyte Infusions (DLI) for CLL – pro

M Levin, MD — Fri, 24 Aug 2012 01:30:23 +0000

Lay Summary: DLI is well studied in chronic myelogenous leukemia but less so in other hematological conditions.

DLI induces complete remissions in the majority of patients with chronic myeloid leukemia (CML) in early-stage relapse and in less than 30% of patients with relapsed acute leukemia, myelodysplasia, and multiple myeloma. DLI-induced remissions of chronic phase CML are durable, but as many as half of patients with other diseases ultimately relapse. Complications of DLI include acute and chronic graft-vs-host disease (GVHD) and aplasia, which induce profound immunosuppression and susceptibility to opportunistic infections. There is a strong correlation of GVHD and disease response.
Other hematologic malignancies do not respond to DLI as well as early-stage CM. In general, less than 30% of patients with relapsed acute leukemia,myelodysplasia, and multiple myeloma achieve complete responses to DLI. As many close to half or more of patients who do achieve a complete response may be expected to relapse after DLI. 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.

Chronic lymphocytic leukemia (CLL) also appears to be responsive to allogeneic donor T cells.However, clinical expereince is limited. Some patient have obtained a remission following DLI as treatment of persistent disease following alloBMT. Other CLL patients have obtained complete remissions, including molecular complete remissions, following discontinuation of posttransplant immunosuppression. Unfortunately, supporting evidence is limited because treatment with CLL with allogeneic transplantation is fairly rare.

Tomblyn, M., & Lazarus, H. M. (2008). Donor lymphocyte infusions: The long and winding road: How should it be traveled? Bone Marrow Transplantation, 42 (9), 569-579.

Deol, A., & Lum, L. G. (2010). Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited. Cancer Treatment Reviews, 36 (7), 528-538.

Treating biphenotypic leukemia – pro

M Levin, MD — Fri, 24 Aug 2012 01:28:02 +0000

A minority of acute leukemias have features characteristic of both the myeloid and lymphoid lineages and for this reason are designated mixed-lineage, hybrid or biphenotypic acute leukemias (BAL). There have been difficulties in establishing whether BAL represents a distinct clinico-biological entity due to a lack of objective criteria for distinguishing BAL from acute myeloid leukemias (AML) or acute lymphoblastic leukemias (ALL) with aberrant expression of a marker from another lineage. As such, it is often treated as AML but with some component of treatment being taken from acute lymphocytic leukemia regimens.There is no agreement on how the disease should be treated. The majority of patients receive treatment according to the morphology of the blasts, with either AML or ALL induction. Cytogenetic abnormalities are observed in a high percentage of bilineal and biphenotypic leukemias. Approximately 33% of cases have the Philadelphia chromosome, and some cases are associated with t(4;11)(q21;q23) or other 11q23 abnormalities. Gleevec can be added in such cases. The basis for such a recommendation is, however, limited, consisting of case reports and one small study that showed minimal response rates(Ahmed et al).

REFERENCES:
Brunning RD, Matutes E, Harris NL, et al.: Acute myeloid leukaemia: introduction. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 77-80.

Aribi, Ahmed et al, Acute leukaemia: a case series.British Journal of Haematology. 138(2):213-216, July 2007.

Molecular Genetic Pathways as Therapeutic Targets in Acute Myeloid Leukemia
ASH Education Book 2008 2008:400-411

Kondo T, Tasaka T, Sano F, Matsuda K, Kubo Y, Matsuhashi Y, Nakanishi H, Sadahira Y, Wada H, Sugihara T, Tohyama K.
Philadelphia chromosome-positive acute myeloid leukemia (Ph + AML) treated with imatinib mesylate (IM): a report with IM plasma concentration and bcr-abl transcripts.Leuk Res. 2009 Sep;33(9):e137-8.

Pier Paolo Piccaluga et al, Imatinib mesylate in the treatment of newly diagnosed or refractory/resistant c-KIT positive acute myeloid leukemia. Results of an italian multicentric phase II study. haematol 2007 92:1721-1722

Pompetti F, Spadano A, Sau A, Mennucci A, Russo R, Catinella V, Franchi PG, Calabrese G, Palka G, Fioritoni G, Iacone A.
Long-term remission in BCR/ABL-positive AML-M6 patient treated with Imatinib Mesylate.Leuk Res. 2007 Apr;31(4):563-7.

Hyper CVAD for Burkitts – pro

M Levin, MD — Fri, 24 Aug 2012 01:24:55 +0000

Standard doxorubicin-based combination chemotherapy, such as CHOP, frequently induces remissions of short duration. The overall CR rate is 915 and induction-therapy mortality was low (6%). In one review the estimated 5-year CR rate was 38% and the estimated 5-year survival rate was 39%. These results were achieved despite broad entrance criteria (no exclusions by age, performance status, organ dysfunction, or infection status at the time of diagnosis). Median age was 39.5 years, about 10 years higher than that of subjects in published studies of adult ALL, and 22% of patients were 60 years or older. In a comparative study, outcome was significantly superior with Hyper-CVAD therapy compared with the VAD regimens, in terms of both CR rate and long-term prognosis.The results from small studies suggest that Rituximab confers additional benefits to patient having DA-EPOCH and Hyper-CVAD. Another popular regimen is Codox-M.
Kluin Nelemans H, Zagonel V, Anastasopoulou A et al. Standard chemotherapy with or without high-dose chemotherapy for aggressive non-Hodgkin’s lymphoma: randomized phase III EORTC study. J Natl Cancer Inst 2001; 93: 22–30K. A. Blum, G. Lozanski, and J. C. Byrd
Adult Burkitt leukemia and lymphoma
Blood, November 15, 2004; 104(10): 3009 – 3020.

S. Smeland, A. K. Blystad, S. O. Kvaloy, I. M. Ikonomou, J. Delabie, G. Kvalheim, J. Hammerstrom, G. F. Lauritzsen, and H. Holte
Treatment of Burkitt’s/Burkitt-like lymphoma in adolescents and adults: a 20-year experience from the Norwegian Radium Hospital with the use of three successive regimens
Ann. Onc., July 1, 2004; 15(7): 1072 – 1078.

H M. Kantarjian, S. O’Brien, T. L. Smith, J. Cortes, F. J. Giles, M. Beran, S. Pierce, Y. Huh, M. Andreeff, C. Koller, et al.
Results of Treatment With Hyper-CVAD, a Dose-Intensive Regimen, in Adult Acute Lymphocytic Leukemia
J. Clin. Oncol., February 1, 2000; 18(3): 547 – 547.

http://www.mccn.nhs.uk/userfiles/documents/Guidelines%20for%20treatment%20of%20Burkitts%20Lymphoma%20DEC%202010.pdf