Cancer Treatment Today » Acute Lymphocytic Leukemia

Velcade for Graft Versus Host DIsease – pro

M Levin, MD — Wed, 16 Oct 2013 21:01:41 +0000

Koreth found that Velcade was beneficial in GVHD; but his was a phase II trial and other phase II trials are ongoing. He found that i the 45 patients who were treated in the study; 89% of patients were treated with a one-locus and 11% of patients were treated with a two-loci mismatch. With a median follow-up of 3 years, the 180-day cumulative incidence of grade 2 to 4 acute GVHD was 22%, and the 1-year cumulative incidence of chronic GVHD was 29%. The non-relapse mortality rate was only 11%, and the relapse rate was 38%. Results were comparable with patients who received HLA-matched transplants with the unexpected observation that bortezomib therapy enhanced immune reconstitution on the basis of measurements of CD8+ T cells and natural killer cells.
The editorial by Giralt that accompanied Koreth report, pointed out that there are four potential current approaches that all are at the same stage of development and that it may be necessary to perform a randomized phase III trial with a short primary end point to be able to rapidly pick a winner from among these competing approaches, one that could be compared with the current standard in a definitive trial.

Koreth J, Stevenson KE, Kim HT, McDonough SM, Bindra B, Armand P, Ho VT, Cutler C, Blazar BR, Antin JH, Soiffer RJ, Ritz J, Alyea EP 3rd. Bortezomib-based graft-versus-host disease prophylaxis in HLA-mismatched unrelated donor transplantation.J Clin Oncol. 2012 Sep 10;30(26):3202-8.

Teresa Caballero-VelázquezPhase II clinical trial for the evaluation of bortezomib within the reduced intensity conditioning regimen (RIC) and post-allogeneic transplantation for high-risk myeloma patients. Phase II clinical trial for the evaluation of bortezomib within the reduced intensity conditioning regimen (RIC) and post-allogeneic transplantation for high-risk myeloma patients, British Journal of Haematology, Volume 162, Issue 4, pages 474–482, August 2013

Koreth J, Stevenson KE, Kim HT, McDonough SM … Antin JH, Soiffer RJ, Ritz J, Alyea EPBortezomib-Based Graft-Versus-Host Disease Prophylaxis in HLA-Mismatched Unrelated Donor Transplantation. J Clin Oncol. 2012 Aug 6

For Lay version see here

Allogeneic Transplant for ALL – pro

M Levin, MD — Sat, 01 Sep 2012 22:17:44 +0000

Lay Summary: The accepted situations that warrant allogeneic transplants for ALL are discussed.

Most current induction regimens for adult acute lymphoblastic leukemia (ALL) include prednisone, vincristine, and an anthracycline. Some regimens also add other drugs, such as asparaginase or cyclophosphamide. Current multiagent induction regimens result in complete response rates that range from 60% to 90%. However some patients relapse and salvage therapy is inadequate for cure. Poor risk ALL is also considered appropriate for consolidation allogeneic transplantation, but NCCN recommends it only when a donor is available (ALL-6).

The goal of stem cell transplantation is to cure the patient’s cancer by destroying the cancer cells in the bone marrow with high doses of chemotherapy and then replacing them with new, healthy blood-forming stem cells.

The accepted benefits of allogeneic hematopoietic cell transplantation (HCT) are due to both the myeloablative chemoradiotherapy and the immune-mediated reaction of donor lymphocytes directed against residual ALL cells in the recipient (ie, the graft-versus-leukemia reaction). To be effective, the survival benefit should outweigh the greater expense and higher risk of early toxicity and death, and late complications such as graft-versus-host disease (GVHD) and sterility. Allogeneic HCT is commonly used as part of the post-remission therapy of patients with ALL demonstrating high-risk features, such as the presence of the Philadelphia (Ph) chromosome or a Ph-like molecular signature [3]. Results have been best when allogeneic HCT is performed in first CR, but allogeneic HCT can also cure some patients in second CR.Franco J. et al, How I treat relapsed childhood acute lymphoblastic leukemia Blood October 4, 2012 vol. 120 no. 14 2807-2816

L.S Muffly et al, Management of Acute Lymphoblastic Leukemia in Young Adults. Clinical Advances in Hematology & Oncology
February 2018 – Volume 16, Issue 2

Goldstone AH, Richards SM, Lazarus HM, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: Final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008; 111(4): 1827-1833The goal of stem cell transplantation is to cure the patient’s cancer by destroying the cancer cells in the bone marrow with high doses of chemotherapy and then replacing them with new, healthy blood-forming stem cells.

L.S Muffly et al, Management of Acute Lymphoblastic Leukemia in Young Adults. Clinical Advances in Hematology & Oncology February 2018 – Volume 16, Issue 2

A 2009(Imrie et al) guideline considers allogenec transplantation appropriate for:

Acute Lymphoblastic Leukemia (ALL) (including lymphoblastic lymphoma)

First complete remission:
Allogeneic stem cell transplantation is an option for patients with ALL with poor prognostic features such as Philadelphia chromosome or t(4;11) positivity or delayed time to first complete remission.
Autologous stem cell transplantation is not recommended for patients with ALL in first complete remission.
Beyond first complete remission:
Allogeneic transplantation is the recommended treatment option for eligible patients with ALL who achieve a second remission.

A 2012 review presented retrospective reviewes and reports that suggest that umbilical cord is as effective as a sibling donor for children with ALL treated with stem cell transplantation but there remain no comparative studies.

There is insufficient evidence to support or refute the use of autologous stem cell transplantation beyond first remission for patients with ALL.

Franco J. et al, How I treat relapsed childhood acute lymphoblastic leukemia Blood October 4, 2012 vol. 120 no. 14 2807-2816
Stem cell transplant for acute lymphocytic/lymphoblastic leukemia (adult). Philadelphia (PA): Intracorp; 2005. Various p. [47 references]

Evidence-based Reviews, American Society of Blood and Marrow Transplantation. 2004. Published in Biology of Blood and Marrow Transplantation and available online at: http://www.asbmt.org/policystat/policy.html

Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993).Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29.

S. Giebel, Hematopoietic Stem Cell Transplantation for Adults With Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in First Remission: A Position Statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2019 Jun;54(6):798-809

L.S Muffly et al, Management of Acute Lymphoblastic Leukemia in Young Adults. Clinical Advances in Hematology & Oncology
February 2018 – Volume 16, Issue 2

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]

Ashfaq K, Yusuf BJ, Jilani AZ, Owais SS, Yahaya I, Chen Y-F, Kinsey SE. Stem cell transplantation for high risk acute lymphoblastic leukaemia in paediatric patients in first remission. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD010348. DOI: 10.1002/14651858.CD010348 – See more at: http://summaries.cochrane.org/CD010348/stem-cell-transplantation-for-high-risk-acute-lymphoblastic-leukaemia-in-paediatric-patients-in-first-remission#sthash.BjAlEfXA.dpuf

EJohn Moore,et al,Equivalent Survival for Sibling and Unrelated Donor
Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia, Biology of Blood and Marrow Transplantation 13:601-607 (2007)

Russell JA, Savoie ML, Balogh A, et al. Allogeneic transplantation for adult acute leukemia in first and second remission with a novel regimen incorporating daily intravenous busulfan, fludarabine, 400 cGy total-body irradiation, and thymoglobulin. Biol Blood Marrow Transplant. 2007; 13(7):814-821.

Schetelig J, Bornhäuser M, Schmid C, et al. Matched unrelated or matched sibling donors result in comparable survival after allogeneic stem-cell transplantation in elderly patients with acute myeloid leukemia: a report from the cooperative German transplant study group. J Clin Oncol. 2008; 26(32):5183-5191.

Kiehl MG, Kraut L, Schwerdtfeger R, et al. Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: No difference in related compared with unrelated transplant in first complete remission. J Clin Oncol. 2004; 22(14):2816-2825.

Revised: 8/22/11

Gleevec for acute lymphocytic leukemia – pro

M Levin, MD — Sat, 01 Sep 2012 22:12:17 +0000

Lay Summary: There is now evidence that GLeevec is very effective in Philadelphia chromosome positive ALL.

Philadelphia-positive ALL is a very difficult disease to treat successfully. In the recent past, the standard approach was to use daunorubicin/vincristine/prednisone-based induction therapy to achieve remission and then, if the patient was a reasonable candidate and a donor could be found, to perform an allogeneic transplant. Now, the use of tyrosine kinase inhibitor therapy may be altering this strategy. Single-agent treatment with imatinib and probably with dasatinib is fairly likely to achieve hematologic responses, but the likelihood of cytogenetic response is lower.

A study reported by Dr. Kirk Schultz on behalf of the Children’s Oncology Group (COG) showed that imatinib mesylate could be given safely in combination with chemotherapy in children with Philadelphia-positive ALL. Patients aged 1-21 with Philadelphia-positive ALL who achieved remission with standard COG induction therapy received an intensive multidrug combination chemotherapy regimen, with introduction of imatinib at 340 mg/m2 for 21 days into an increasing number of treatment blocks in successive cohorts of patients. Patients receiving imatinib had a higher incidence of transaminase elevation in first consolidation and maintenance. However, there were few significant additional increased toxicities compared with historical and contemporaneous controls not receiving imatinib. This appeared to be a feasible combination of a targeted therapy with chemotherapy and will be explored further in subsequent trials.

Dr. Deborah Thomas, a pioneer in the use of imatinib mesylate and chemotherapy in adults with Philadelphia-positive ALL, presented her most recent data at ASH 2007. This is the Phase II Pilot Study of Intensified Chemotherapy With or Without Allogeneic Hematopoietic Stem Cell Transplantation in Children With Very High-Risk Acute Lymphoblastic Leukemia. The chemotherapy backbone was the MD Anderson standard of hyper-CVAD, which is fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and high-dose ara-C. Although a high rate of remission was achieved historically with the use of this regimen in patients with Philadelphia-positive ALL, disease-free survival was brief. Dr. Thomas and colleagues added imatinib at 400 mg per day on days 1 through 14 to each of 8 courses followed by 12 months of imatinib. In later iterations of her work, imatinib was increased to 600 mg per day on days 1 through 14 for courses 1 through 8, with imatinib being given indefinitely after maintenance was completed. Overall, 52 patients with imatinib-naive or minimally treated Philadelphia-positive ALL received therapy from April 2001 to July 2006. With a 3-year treatment follow-up, there were only 7 relapses (14%); however, 12 patients died. The 3-year remission and disease-free survival rates for the combination compared favorably with hyper-CVAD alone (83% vs 24%, and 55% vs 14%, respectively).

Schultz KR, Aledo A, Bowman WP, et al. Minimal toxicity of imatinib mesylate in combination with intensive chemotherapy for Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) in children: a report of the Children’s Oncology Group (COG) AALL0031 protocol for very high risk ALL. Blood. 2006;108:87a. Abstract 283.
Thomas DA, Faderl S, Cortes J, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004;103:4396-4407
Oliver G. Ottmann andBarbara WassmannTreatment of Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia ASH Hematology 2005© 2005 The American Society of Hematology

Overview of treatment options for acute lymphocytic leukemia – pro

M Levin, MD — Sat, 01 Sep 2012 22:10:32 +0000

Children with acute lymphocytic leukemia (ALL) who undergo treatment have about an 80 percent cure rate. Newer treatments may soon boost the child cure rate to as high as 90 percent. Adults have around a 40 percent cure rate. Individuals who fall in the adolescent group can be elgitimately treated with children’s protocols or as adults.

Induction therapy. The purpose of the first phase of treatment is to kill most of the leukemia cells in the blood and bone marrow.
Consolidation therapy. Also called post-remission therapy, this phase of treatment is aimed at destroying the leukemia cells remaining in the brain or spinal cord. Extra spinal taps and radiation therapy are considered crucial during this phase to decrease the risk of relapse.
Maintenance therapy. The third phase of treatment prevents leukemia cells from regrowing. The treatments used in this stage are often given at much lower doses.

Children with acute lymphocytic leukemia typically receive treatment to kill leukemia cells hiding in the central nervous system during each phase of therapy. This is called central nervous system sanctuary therapy, central nervous system preventive therapy or intrathecal chemotherapy. In this type of chemotherapy, anti-cancer drugs are injected directly into the fluid that covers the spinal cord. The drugs used here are methotrexate and Ara-C.

The three phases of treatment typically take two and a half to three and a half years. Chemotherapy is the major form of remission induction therapy for children and adults with acute lymphocytic leukemia. It usually lasts about four weeks, sometimes longer.

Children with standard-risk ALL usually receive three drugs for the first month of treatment — vincristine, L-asparaginase, and a corticosteroid such as prednisone or dexamethasone. Children in the high-risk group may also receive an anthracycline drug such as daunorubicin. Adults with ALL receive a similar combination that usually includes vincristine, a corticosteroid and an anthracycline drug.

Some of these same medications are also used in the consolidation and maintenance phases. However, the later phases usually rely on less intensive regimens that don’t require staying in the hospital.

Gleevec and stem cell transplantation is not reviewed in this brief post.

Samuel ED, Sakamoto KM.. Topics in pediatric leukemia–acute lymphoblastic leukemia. MedGenMed. 2005 Mar 7;7(1):23

Redaelli A. A systematic literature review of the clinical and epidemiological burden of acute lymphoblastic leukaemia (ALL). Eur J Cancer Care. 2005;14(1):53-62.

Rowe JM. Induction therapy for adults with acute lymphoblastic leukemia (ALL): results of over 1,500 patients from the international ALL Trial: MRC UKALL XII / ECOG E2993. Blood. 2005;Aug 16

The role of flow cytometry in diagnosis of acute leukemia – pro

M Levin, MD — Sat, 01 Sep 2012 22:07:06 +0000

Acute leukemia displays characteristic patterns of surface antigen expression (CD antigens), which facilitate their identification and proper classification and hence play an important role in instituting proper treatment plans. In addition to enzyme cytochemical analysis, multiparameter flow cytometric analysis has become commonplace in most laboratories for that purpose. Aside from identification of blasts, flow cytometry is especially useful in the correct identification of AML MO, differentiation of APL from AML M1/M2, and correct identification of TdT-negative ALL and unusual variants, such as transitional B-cell ALL and undifferentiated and biphenotypic acute leukemias. Distinction between lymphoid and myeloid leukemias, most often made by flow cytometry, is crucially important. Several advances in flow cytometry, including availability of new monoclonal antibodies, improved gating strategies, and multiparameter analytic techniques, have all dramatically improved the utility of flow cytometry in the diagnosis and classification of leukemia.

Flow cytometery is very helpful in a diagnosis of any leukemic condition but is most useful for differentiating different leukemia subtypes. Final diagnosis should never relay on one report alone but should be produced by a consideration of clinical findings and history, examination of the peripheral smear and bone marrow morphology, and, if necessary special stains. Flow cytometery represents one of several sources of information that go into making a secure diagnosis. It should not be relied on in isolation to make a diagnosis.

More recenlty, it is being sued for the dteection of MRD (min ressidual disease).

However, this patient is now in a remission s/p transplant. Use of flow cytometery in surveillance and followup is not well explored and not generally accepted.
There are no guidelines that support it.

Kaleem, Zahid, Crawford, Eric, Flow cytometric analysis of acute leukemias: Diagnostic utility and critical analysis of data Arch Pathol Lab Med. 2003;127:42-48

Belurkar S, Mantravadi H, Manohar C, Kurien A. Correlation of morphologic and cytochemical diagnosis with flowcytometric analysis in acute leukemia. J Cancer Res Ther. 2013;9(1):71.

Jie Xu, MD, PhD, Jeffrey L. Jorgensen, MD, PhD, Sa A. Wang, MD et al, How Do We Use Multicolor Flow Cytometry to Detect Minimal Residual Disease in Acute Myeloid Leukemia? Clin Labor Med December 2017Volume 37, Issue 4, Pages 787–802

IVIG post transplantation – pro

M Levin, MD — Sat, 01 Sep 2012 20:49:01 +0000

Intravenous gammaglobulin is often administered after bone marrow/ stem cells transplantation to prophylax for infections. Antibiotics and intravenous gamma globulin are often adminstered for at least 100 days after transplant to decrease the risk of bacterial infection immediately following transplant. Although there are no randomized studies of this strategy, it is recommended by the joint guidelines of CDC, the Infectious Disease Society of America, and the American Society of Blood and Bone Marrow Transplantation. For actually hypogammaglobulinemic patients a higher dose is used than than is standard for non-HSCT recipients because the IVIG half-life among HSCT recipients (generally 1–10 days) is much shorter than the half-life among healthy adults (generally 18–23 days) (therefore, the IVIG dose for a hypogammaglobulinemic recipient should be individualized to maintain trough serum IgG concentrations >400–500 mg/dl (should monitor trough serum IgG concentrations among these patients approximately every 2 weeks and adjust IVIG doses as needed.

In their recently published meta-analysis of prophylactic intravenous immunoglobulin (IVIG) in allogeneic stem cell transplantation (alloSCT), Raanani et al concluded that IVIG does not have a role in SCT. The debate continues but guidelines currently recommend it.

Stanley C. Jordan, Ashley A. Vo, Mieko Toyoda, Dolly Tyan, Cynthia C. Nast (2005)
Post-transplant therapy with high-dose intravenous gammaglobulin: Applications to treatment of antibody-mediated rejection Pediatric Transplantation 9 (2), 155–161.

Antin, JH. Long-term care after hematopoietic-cell transplantation in adults. N Engl J Med. 2002; 347(1):36-42.

Uptodate, Prevention of infections in hematopoietic cell transplant recipients, 2016
.
Andrew J. Ullmann et al, Published online 2016 Jun 24. Infections in haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016. Ann Hematol. 2016; 95: 1435–1455

Raanani P, Gafter-Gvili A, Paul M, et al: Immunoglobulin prophylaxis in hematopoietic stem cell transplantation: Systematic review and meta-analysis. J Clin Oncol 27:770-781, 2009

History of stem cell and bone marrow transplantation in cancer and leukemia – pro

M Levin, MD — Sat, 01 Sep 2012 02:24:00 +0000

The history of stem cell research includes work with both animal and human stem cells. Stem cells can be classified into three broad categories, based on their ability to differentiate. Totipotent stem cells are found only in early embryos. Each cell can form a complete organism (e.g., identical twins). Pluripotent stem cells exist in the undifferentiated inner cell mass of the blastocyst and can form any of the over 200 different cell types found in the body. Multipotent stem cells are derived from fetal tissue, cord blood, and adult stem cells.

A prominent application of stem cell research has been bone marrow transplants using adult stem cells. Among early attempts to do this were several transplants carried out in France following a radiation accident in the late 1950′s. Since physicans could not isolate stem cells at that time, they transfused bone marrow with stem cells in it. Autologous marrow means from the same individual while allogeneic marrow is provided by another individual. A bone marrow transplant between identical twins guarantees complete HLA compatibility between donor and recipient. These were the first kinds of transplants in humans, followed by autologous transplants. It was not until the 1960′s that physicians knew enough about HLA compatibility to perform transplants between siblings who were not identical twins. In 1973 a team of physicians performed the first unrelated bone marrow transplant. In 1984 Congress passed the National Organ Transplant Act, which among other things, included language to evaluate unrelated marrow transplantation and the feasibility of establishing a national donor registry. This led ultimately to National Marrow Donor Program (NDWP) a separate non-profit organization that took over the administration of the database needed for donors in 1990. The 1990′s saw rapid expansion and success of the bone marrow program with more than 16,000 transplants to date for the treatment of immunodeficiencies and leukemia.

Now that stem cells can be harvested from the blood, stem cell transpalntation has largely replaced bone marrow transplantation, although recent trials have revived an interest in bone marrow trnasplantation and its possible advantages over stem cell transplants. Adult stem cells also have shown great promise in other areas. Stem cell transplant for acute myelogenous leukemia. Philadelphia (PA): Intracorp; 2005. Various p. [50 references]

http://www.emedicine.com/med/topic3497.htm

Buckner CD: Autologous bone marrow transplants to hematopoietic stem cell support with peripheral blood stem cells: a historical perspective. J Hematother 1999 Jun; 8(3): 233-6

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).

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

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.
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