Cancer Treatment

Tandem transplants for testicular cancer

High dose chemotherapy with autologous stem cell rescue is an accepted and standard of care approach for relapsed or nonresponig testicualr cancer. It is recommended by several guidelines, including NCCN. however, they do not address single versus tandem transplants. A tandem transplant is on that has a pre-planned second transplant with another infusion of stem cells after competion and recovery from the first transpalnt procedure.There are no prospective studies but retrospective reviews from Indiana University, which has the largest referral base of germ cell tumors in the world suggest that tandem transplantation for testicular cancer is the treatment of choice for this malignancy. A review form the CLeveland clnic concludes: " Tandem autotransplants for testicular cancer are associated with less treatment-related mortality than a planned single transplant, with no differences in disease-related outcomes or overall survival at 3 years. Patient selection bias for either transplant approach, however, may affect the results of this observational study; a randomized trial is needed to determine which approach, if either, is better."

Einhorn L, Williams S, Chamness a, et al. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. New England Journal of Medicine. 2007;357:340-348.

NCCN.ORG, Testicular, p.16

http://www.uroweb.org/fileadmin/tx_eauguidelines/22891_Testicular_Cancer.pdf

Lazarus HM, Stiff PJ, Carreras J, Logan BR, Akard L, Bolwell BJ, Childs RW, Gale RP, Klein JP, Lill MC, Pérez WS, Stadtmauer EA, Rizzo JD.Utility of single versus tandem autotransplants for advanced testes/germ cell cancer: a center for international blood and marrow transplant research (CIBMTR) analysis.Biol Blood Marrow Transplant. 2007 Jul;13(7):778-89.

Stem Cell Transplantation for Scleromyxedema.

Scleromyxedema is characterized by a generalized papular and sclerodermatous eruption, monoclonal gammopathy in the absence of thyroid disease, and evidence of mucin deposition, fibrosis, and particularly skin involvement.Scleromyxedema is similar to scleroderma, but has predominantly mucin deposition and is usually associated with a serum IgG monoclonal paraprotein. High-dose chemotherapy with stem cell rescue is feasible for patients with scleromyxedema and, although not curative, offers durable remission in most patients. The available evidence is that of case reports and series, which is understandable given the rarity of the disease.

There are no guidelines, consensus sttements or review articles that recommend this therapy. However, the provided plan language does not contain anything that excludes this procedure. It is apparently effective for pallation but not cure based on the current literature, albeit this literature is limited.It is not in trials and could never be.

However, this condition can be seen as a form of scleroderma. Stem cell transplantation in the hope of modifying disease activity in scleroderma is under active clinical investigationl.As previously pointed out, the low ejection fraction makes this procedure riskier.

Adrienne M. Feasel, MD; Michele L. Donato, MD; Madeleine Duvic, MDComplete Remission of Scleromyxedema Following Autologous Stem Cell Transplantation Arch Dermatol. 2001;137:1071-1072.

C . Cokonis Georgakis , G . Falasca , A . Georgakis , W . Heymann Scleromyxedema . 
Clinics in Dermatology , Volume 24 , Issue 6 , Pages 493 - 497 2006

Lacy MQ, Hogan WJ, Gertz MA, Dispenzieri A, Rajkumar SV, Hayman S, Kumar S, Litzow MR, Schroeter AL.Successful treatment of scleromyxedema with autologous peripheral blood stem cell transplantation.Arch Dermatol. 2005 Oct;141(10):1277-82

Complete Remission of Scleromyxedema Following Autologous Stem Cell Transplantation Am Acad Dermatol. 2004 Jul;51(1):126-31 Adrienne M. Feasel, MD; Michele L. Donato, MD; Madeleine Duvic, MD

van Laar JM, Farge D, Tyndall A. Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial: hope on the horizon for patients with severe systemic sclerosis. Ann Rheum Dis 2005; 64:1515.

van Laar JM, Tyndall A. Adult stem cells in the treatment of autoimmune diseases. Rheumatology (Oxford) 2006; 45:1187-1193.

Alan Tyndall; Daniel E. Furst Adult Stem Cell Treatment of Scleroderma Curr Opin Rheumatol.  2007;19(6):604-610

 

Autologous stem cell transplant for follicular lymphoma

Lay Summary:

The role of AuSCT is not entirely clear in follicular lymphoma.

There are now 3 conflicitng studies of autologous transplant for follicular lymphoma.

Despite nearly identical eligibility criteria and the use of an anthracycline-based induction treatment in all studies, the results are quite different. The previous studies found a significant advantage to autologous stem cell transplantation (ASCT). The German Lymphoma Study Group (GLSG) reported that patients randomized to transplantation had a 64.7% progression-free survival (PFS) rate at 5 years versus 33% with conventional chemotherapy. The Groupe Ouest-Est d'Etude des Leucémies aigues et autres Maladies du Sang (GOELAMS) group reported 60% PFS for those randomized to autologous transplantation versus 48% with conventional chemotherapy. By contrast, the Groupe d'Etude des Lymphomes de l'Adulte (

GELA

) study does not show a significant PFS advantage for autologous transplantation.

The overall role of ASCT in follicular lymphoma continues to be debated. It is an excellent treatment option for the management of younger patients with recurrent disease. In advanced newly diagnosed lymphoma, a survival advantage has yet to be shown; with more prolonged follow-up it may still emerge in the GLSG study. An increased risk for therapy-related acute myeloid leukemia (t-AML) was observed in the GLSG and GOELAMS studies, but this risk may be minimized by modulation of induction and mobilization therapy preceding transplantation. Despite spectacular advances since the introduction of rituximab, many patients with advanced disease and a high Follicular Lymphoma International Prognostic Index (FLIPI) score have disease recurrences. For such patients, the continued study of autologous transplantation, possibly in combination with rituximab for in vivo purging, remains an important area of investigation.

In conclusion, there is no consensus regarding autologous stem ell transplantation for follicular lymphoma. Since some experts lukewarmy advocate it, it should not be considered "not medically necessary', even if it is arguably still investigational.

Koen van Besien Autologous transplantation for follicular lymphoma? Not too soon! Blood, 15 October 2006, Vol. 108, No. 8, pp. 2496-2497.

NCCN.ORG

Stem Cell Transplant for relapsed acute myelogenous leukemia

Refractory and relapsed disease occurs in most acute myelogenous leukemia patients. Salvage chemotherapy offers a 30–70% chance of a second complete remission. Unfortunately, this second remission is usually short lived and salvage chemotherapy is rarely curative. Allogeneic bone marrow transplant, either human leukocyte antigen (HLA)-sibling matched or matched unrelated donor, is the only treatment to offer long-term disease-free survival and possible cure.  Allogeneic transplantation is standard of care after AML relapse.

Estey EH. Therapeutic options for acute myelogenous leukemia.Cancer. 2001 Sep 1;92(5):1059-73.

nccn.org, AML

Socie G. Current issues in allogeneic stem cell transplantation. Hematology. Sep-Oct 2005;10 Suppl 1:63.

Bloodless stem cell transplants

With an estimated 6000000 Jehovah's witnesses worldwide, haematologists may encounter patients who decline blood transfusions as a matter of personal belief.The risks of high-dose chemotherapy include life threatening bleeding from thrombocytopenia and profound anemia. Autologous stem cell transplantation is usually associated with the transfusion of 5 to 20 units of red blood cell or platelets, with the potential side-effects of infectious disease transmission, transfusion reactions, and iron overload. Inabilty ot ransfuse can be accommodates by increasing sue o erythropoietin (although this was shown in one study not to change outcomes), minimizing blood collection and blood sparing techniques.

In recent years, several facilites, such as University of Pennsylkvanis,  have extended their bloodles surgery programs into the area of transplantation. However, this remains supported by case reports abd series only. It might be expected that only successful cases are published since a publication bias applies in this situation. It is also likely that some conditions are less suitable to this approach and this, as well as apropriate patietn selection,  must be explored in clinical trials.

K K Ballen et al,  Case Report  Successful autologous bone marrow transplant without the use of blood product support July 2000, Volume 26, Number 2, Pages 227-229

Estrin JT, Ford PA, Henry DH et al. Erythropoietin permits high-dose chemotherapy with peripheral blood stem-cell transplant for a Jehovah's Witness. Am J Hematol 1997; 55: 51-52

Bone Marrow Transplant. 2008 Feb 4 [Epub ahead of print] Links
SCT in Jehovah's Witnesses: the bloodless transplant.Sloan JM, Ballen K..

Tendem and singel stem cell transpalntation for ovarian germ cell tumors

The role of stem cell transplntation for ovarian germ cell tiumors is evolving. The European Group for Blood and Marrow Transplantation (Urbano-Ispizua et al, 2002) recently stated that for ovarian cancer with minimal residue disease, allogeneic transplantation is not generally recommended; while autologous transplantation may be undertaken in approved clinical protocols -- the value of transplants for patients included in this category needs further investigation. For refractory ovarian cancer, allogeneic transplantation using sibling donor is developmental (there is very little experience with this particular type of transplant); while allogeneic transplantation using alternative donor or autologous transplantation is not generally recommended. For relapsed germ cell tumors that were sensitive to chemotherapy, allogeneic transplantation is not generally recommended, while autologous transplantation is standard use in selected patients. For refractory germ cell tumors, allogeneic transplantation is not generally recommended; while autologous transplantation may be undertaken in approved clinical protocols.

Transplantation is being tested in poor-risk germ cell tumors in both males and females but trials so far do not show that it is superior to chemotherapy alone.

Research on the role of autologous verus allogneeic and on schedule and preparative regimens transplantation in germ cell tumors is still ongoing. There is little known on tandem or 2nd transplants for this patient population and such transpalnt asre certainly experiemental at the present time.

http://clinicaltrialssearch.org/combination_chemotherapy_plus_peripheral_stem_cell_transplantation_in_treating_patients_with_germ_cell_tumors.html

R. J. Motzer, C. J. Nichols, K. A. Margolin, J. Bacik, P. G. Richardson, N. J. Vogelzang, D. F. Bajorin, P. N. Lara Jr, L. Einhorn, M. Mazumdar, et al.
Phase III Randomized Trial of Conventional-Dose Chemotherapy With or Without High-Dose Chemotherapy and Autologous Hematopoietic Stem-Cell Rescue As First-Line Treatment for Patients With Poor-Prognosis Metastatic Germ Cell Tumors
J. Clin. Oncol., January 20, 2007; 25(3): 247 - 256.

http://nccn.org/professionals/physician_gls/PDF/ovarian.pdf

Mycoisis fungoides and Sezary (CTCL) and stem cell transplantation

Cutaneous T-cell lymphoma (CTCL) is classified as an indolent hematologic malignancy with distinct clinicopathologic features. Although prognosis varies depending on the stage, patients who have cutaneous tumor, lymph node or visceral involvement, or peripheral blood involvement (Sézary syndrome) generally have a poor outcome.
Evidence for stem cell transplantation, both autologous adn allogeneic is on the level of case reports. Experts agree that more investigtioan is needed.

Y. Oyama, J. Guitart, T. Kuzel, R. Burt, S. RosenHigh-dose therapy and bone marrow transplantation in cutaneous T-cell lymphoma. 
Hematology/Oncology Clinics of North America, Volume 17, Issue 6, Pages 1475-1483, 2003.
Whittaker SJ, Marsden JR, Spittle M, Russell Jones R. Joint British Association of Dermatologists and U.K. Cutaneous Lymphoma Group guidelines for the management of primary cutaneous T-cell lymphomas. Br J Dermatol 2003 Dec;149(6):1095-107. [67 references

Chemotehrapy for medulloblastoma in adults

Medulloblastoma is treated primarily with surgical excision followed by radiation therapy and chemotherapy. When there is spinal extension, craniospinal radiation is standard.

Inoperable medulloblastomas are often treated iwth chemotherapy but there is no randomized prospective evidence to support this. This is especially so in adults, in whom this disease is much less common and in whom it appears to behave distinctly differently. 30% of cases occur in adults. Recent therapeutic advances in the treatment of average-risk childhood medulloblastoma have emphasized the reduction of treatment-related toxicity while improving progression-free survival and high dose therapy. However, lessons learned from the pediatric experience have not been widely applied to the adult population in Phase II or randomized clinical trials.

nccn.org, brain cancer

David D Eisenstat Clinical management of medulloblastoma in adults
Expert Review of Anticancer Therapy October 2004, Vol. 4, No. 5, Pages 795-802

http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/NeuroOncology/ManagementPolicies/Medulloblastoma.htm

Granulocute Transfusions

Lay Summary: An ssessment of the role of granulocyte transfusions in 2008.

Granulocyte transfusions are requested by clinicians for use in patients with refractory infection or at high risk of developing severe infection (Strauss 2003). Most patients prescribed granulocyte transfusions are those with cancer related neutropenia, who are receiving myeloablative chemotherapy with or without haemopoietic stem cell rescue. Interest in the use of granulocytes remains high (Van Burik & Weisdorf, 2002; Price 2006), and requests for granulocyte components for transfusion have steadily increased in England and Wales during the last five years. This has been driven by publications describing transfusion in neutropenic patients both for therapeutic indications, when they have an infection refractory to antimicrobials (Hubel et al. 2002) and for secondary prophylaxis, in patients who have had severe bacterial or fungal infections previously but who require a further cycle of chemotherapy or haemopoietic stem cell rescue (Kerr et al. 2003, Oza et al., 2006). Recent studies with promising but overall inconclusive results have been reported both in adults (Oza et al., 2006) and children (Sachs et al., 2006).

The exact clinical role for granulocyte transfusions (whether derived from whole blood or collected by apheresis) therefore remains unclear. Potential efficacy including a dose dependent effect has been raised by systematic reviews/meta-analyses (Vamvakas et al. 1996; Vamvakas et al. 1997; Stanworth et al., 2004), and in animal studies. The existing literature is, perhaps not surprisingly, otherwise heavily dominated by case reports and small case series, with the significant attendant risk of publication bias. However, it should be acknowledged that anecdotal evidence of benefit in selected patients from physicians in the UK and abroad can be found, and that a number of very recent publications have again pointed to evidence of benefit, including one study based on biological randomisation - although this study was underpowered to detect an effect on mortality (Oza et al., 2006).

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

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 amrrow 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