Cancer Treatment Today » Allogeneic Stem Cell Transplantation

DLI for T cell leukemia and lymphoma – pro

M Levin, MD — Fri, 10 Jan 2014 16:27:04 +0000

Donor lymphocyte infusions are designed to awaken some degree of graft versus host reaction, which contains within it also the graft versus disease effect. It is a modality that can be used after allogeneic transplantation to treat relapse by “awakening” an immune response. . Almost all work on DLI was in B cell leukemias and lymphomas. How it affects T cell malignancies is not well studied and most of what is known was in Adult T-Cell leukami/Lymphoma. Many questions remain. For example, achieving hematologic remission with DLI is not an easy task, especially in patients with a high tumor burden and rapidly proliferating leukemic cells.. Cytoreductive therapy before DLI is thought to improve effectiveness of DLI. Unfortunately, which regimens to use for this cytoreduction has not been defined. How to induce and manage graft versus host reaction has not been defined. Even the very effectiveness of allogeneic transplantation in T-Cell Leukemias continues to be studied. To conclude, DLI remains experimental for T Cell malignancies due to lack of reliable information on how to do it and how effective it is.

Hidehiro Itonag et al, Treatment of relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation: the Nagasaki Transplant Group experience Blood January 3, 2013 vol. 121 no. 1 219-225

Gabriel IH. Graft versus lymphoma effect after early relapse following reduced-intensity sibling allogeneic stem cell transplantation for relapsed cytotoxic variant of mycosis fungoides. Bone Marrow Transplant 2007;40(4):401-403.

Herbert KE, . Graft-versus-lymphoma effect in refractory cutaneous T-cell lymphoma after reduced-intensity HLA-matched sibling allogeneic stem cell transplantation. Bone Marrow Transplant 2004;34(6):521-525.

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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

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Rituxan for PTLD -pro

M Levin, MD — Thu, 25 Apr 2013 18:23:26 +0000

Post-transplant lymphoproliferative disease (PTLD) remains a major complication after solid organ and allogeneic stem cell transplantation. It is usually related to outgrowth of lymphocytes infected with Epstein-Barr virus (EBV). Following titers and an individualized treatment plan including decreased immunosuppression and other agents should be chosen based on the severity and extent of disease.

Some classify PTLD into three groups(1): Early lesion (ie, plasmacytic hyperplasia and infectious mononucleosis-like PTLD), Polymorphic PTLD and Monomorphic PTLD Monomorphic PTLD. Rituxan appears to have some role in the management of this condition. Several studies show that it reduces both the titers and severity of PTLD. It can be given by itself of with low dose chemotherapy(2).

The strategy of following titers and giving prophylactic Rituxan has not been formally studied. Most published studies have dealt with treating patients who already have PTLD.

1.Swerdlow SH, Campo E, Harris NL, et al. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.

2.Gross TG, Orjuela MA, Perkins SL, Park JR, Lynch JC, Cairo MS, Smith LM, Hayashi RJ.Low-dose chemotherapy and rituximab for posttransplant lymphoproliferative disease (PTLD): a Children’s Oncology Group Report. Am J Transplant. 2012 Nov;12(11):3069-75.

3.Jain AB, Marcos A, Pokharna R, Shapiro R, Fontes PA, Marsh W, Mohanka R, Fung JJ.Rituximab (chimeric anti-CD20 antibody) for posttransplant lymphoproliferative disorder after solid organ transplantation in adults: long-term experience from a single center. Transplantation. 2005 Dec 27;80(12):1692-8.

5..N. Milpied et al, Humanized anti-CD20 monoclonal antibody (Rituximab) in post transplant B-lymphoproliferative disorder: A retrospective analysis on 32 patients Medicine, Annals of Oncology
Volume 11, Issue suppl 1, Pp. S113-S116.

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Graft versus host disease (GVHD) prophylaxis – pro

M Levin, MD — Fri, 05 Oct 2012 16:25:54 +0000

Calcineurin inhibitors, such as cyclosporine and tacrolimus, are commonly used in the prophylaxis of GvHD (BCH guideline). For full-intensity stem cell transplantation most centres use a combination of a calcineurin inhibitor, such as ciclosporin or tacrolimus, given in combination with methotrexate. Low-dose methotrexate was the first generally prescribed GVHD preventive regimen for use as a cell-cycle specific chemotherapeutic agent following transplant and was subsequently combined with a T cell activation inhibitor, such as cyclosporin and tacrolimus. Calcineurin inhibitor-based regimens are now the most common form of GVHD prophylaxis. The majority of clinical trials over the past decades have shown the superiority of combination of a calcineurin inhibitor and a short course of methotrexate over either agent alone in the reduction of GVHD incidence and improvement in survival. A meta-analysis of prophylaxis regimens for GVHD also supports the use of cyclosporin-methotrexate over cyclosporin alone.

Bhurani D, Schifter M, Kerridge I. Folinic acid administration following MTX as prophylaxis for GVHD in allogeneic HSCT centres in Australia and New Zealand.Bone Marrow Transplant. 2008 Oct;42(8):547-50.

Ross M, Schmidt GM, Niland JC, et al. Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prevention of acute graft-vs.-host disease: Effect on chronic graft-vs.-host disease and long-term survival. Biol Blood Marrow Transplant. 1999;5:285-291.

http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.med.54.101601.152456

http://www.bcshguidelines.com/documents/BCSH_Guideline_Acute_GVHD_diagnosis_and_management_v1.pdf

http://bestpractice.bmj.com/best-practice/monograph/946/treatment/step-by-step.html, 2012

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Busulfan, fludarabine and thymogen (ATG) as conditioning for allogeneic stem cell transplantation – pro

M Levin, MD — Fri, 05 Oct 2012 12:30:23 +0000

The regimen of busulafan. fludarabine and thymogen has been very quickly adopted and now studies of it as a base for adding additonal drugs have been initiated. However, there is room for caution. Thymoglobulin added to busulfan and fludarabine to conditioning before an allogeneic stem cell transplant may reduce the incidence and severity of graft versus host disease, especially in matched unrelated graft, but it can potentially promote higher reapse rates. In a retrospective review, Bredeson found exactly such an outcome. A recent study(McCune et al) confirmed low GVHD rates for this conditioning regimen and concluded: “The low rates of GvHD, particularly in its chronic form, were encouraging, and further biomarker studies are warranted to optimize the fludarabine/Tbusulfan/rATG conditioning regimen.” It stands to reason that mores studies on relapse rates should be performed before wide scale adoption of the addition of thymogen to busulfan-fludarabine.

A 2012 guideline (Fischmann et al) says this: “Our systematic review suggests that the addition of ATG during allogeneic HSCT significantly reduces the incidence of severe grades (II to IV) of acute GvHD, whereas the incidence of overall acute GVHD (grades I to IV) was not significantly lowered. This indicates a reduction of the severity but not the incidence of acute GVHD. However, this effect did not lead to a significant improvement of overall survival, which may be due to the severe potential side effects of the consecutively increased immunosuppression.Furthermore, future research is needed to clarify the effect of ATG on the incidence and severity of chronic GVHD and consequently on all aspects of quality of life.From the currently available data, no recommendation on the general use of ATG in allogeneic HSCT can be supported.

Theurich S, Fischmann H, Shimabukuro-Vornhagen A, Chemnitz JM, Holtick U, Scheid C, Skoetz N, von Bergwelt-Baildon M. Polyclonal anti-thymocyte globulins for the prophylaxis of graft-versus-host disease after allogeneic stem cell or bone marrow transplantation in adults.Cochrane Database Syst Rev. 2012 Sep 12;9:CD009159.

Bredeson CN, Zhang MJ, Agovi MA, Bacigalupo A, Bahlis NJ, Ballen K, Brown C, Chaudhry MA, Horowitz MM, Kurian S, Quinlan D, Muehlenbien CE, Russell JA, Savoie L, Rizzo JD, Stewart DA. Outcomes following HSCT using fludarabine, busulfan, and thymoglobulin: a matched comparison to allogeneic transplants conditioned with busulfan and cyclophosphamide.Biol Blood Marrow Transplant. 2008 Sep;14(9):993-1003.

Jeannine S. McCune, Erica L. Woodahl, Terry Furlong, Barry Storer, Joanne Wang, Shelly Heimfeld, H. Joachim Deeg and Paul V. O’Donnell, A pilot pharmacologic biomarker study of busulfan and fludarabine in hematopoietic cell transplant recipients Cancer Chemotherapy and Pharmacology Volume 69, Number 1 (2012), 263-272

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Prophylactic Acyclovir after stem cell transplantation – pro

M Levin, MD — Tue, 25 Sep 2012 15:44:28 +0000

Both allogeneic and autologous hematopoietic cell transplant (HCT) recipients are at increased risk for a variety of infections based upon their degree of immunosuppression and exposures, more so the allogeneic transplant recipients.
The types of infections to which these hosts are most vulnerable can be roughly divided based upon their temporal relation to the transplantation:

Preengraftment — less than three weeks
mmediate postengraftment — three weeks to three months
Late postengraftment — more than three months

Unfortunately, infection is reported as the primary cause of death in 8% of autologous HCT patients and 17% to 20% of allogeneic HCT recipients. Many of these are CMV or varicela-zoster infections. High-dose intravenous acyclovir (500 mg/m2 3 times
daily, from day < 5 until day > 30) followed by oral acyclovir (800 mg 4 times daily for 6 months) has been found to effectively reduce the incidence of CMV disease (52%–59% vs. 61%–75%) and increase overall . patient survival. The Infectious Diseases Society of America (IDSA) issued clinical practice guidelines for preventing opportunistic infections among HCT recipients, published in Biol Blood Marrow Transpant ; 2009 ; 15 : 1143 -1238. IDSA does not recommend open ended acyclovir prophylaxis. It says: “Acyclovir prophylaxis should be offered to all HSV-seropositive allogeneic recipients to prevent HSV reactivation during the early posttransplant…Ganciclovir, high-dose acyclovir, and valacyclovir have all shown efficacy in randomized studies in reducing the risk for CMV infection after HCT period (AI). The standard approach is to begin acyclovir prophylaxis at the start of the conditioning therapy and continue until engraftment occurs or until mucositis resolves, whichever is longer, or approximately 30 days after HCT.” It does appears from its discussion in this section that there may be a benefit for a longer patients who are seropositive for CMV or VZV but the guideline does not define how long and does not specifically recommend it. NCCN does recommend a year of prophylaxis in CMV or VZV infected patients but otherwise only for 30 days. American Society of Bone Marrow Transplantation and CDC take the same position in an identical language to the ISDA.

http://www.idsociety.org/Other_Guidelines/

Michael Angarone et al,Prevention and Early Treatment of Opportunistic Viral Infections in Patients With Leukemia and Allogeneic Stem Cell Transplantation Recipients, J Natl Compr Canc Netw 2008;6:191-201

Prentice HG, Gluckman E, Powles RL, et al. Impact of long-term acyclovir on cytomegalovirus infection and survival after allogeneic
bone marrow transplantation. European Acyclovir for CMV Prophylaxis Study Group. Lancet 1994;343:749–753.

NCCN, Prevention and Treatment of Cancer Related Infections, INF-3, 2012

Marcie Tomblyn, Tom Chiller, Hermann Einsele, Ronald Gress, Kent Sepkowitz, Jan Storek, John R. Wingard, Jo-Anne H. Young, Michael A. Boeckh
Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective Biol Blood Marrow Transplant 15: 1143-1238 (2009) 2009 American Society for Blood and Marrow Transplantation

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Prostate Px – pro

M Levin, MD — Thu, 13 Sep 2012 14:25:43 +0000

Risk assessment can be useful to clinicians because it allows assessment of risk versus benefit of partcular treatments. Risk assessment methods currently used for newly diagnosed prostate cancer patients have disadvantages. THey include: D’Amico risk categories, Partin probability tables, University of California, San Francisco-Cancer of the Prostate Risk Assessment risk score, and Kattan nomograms; all rely heavily on traditional clinical variables (eg, serum prostate-specific antigen level, Gleason score, and clinical stage) to estimate risk of various outcomes. Using nomograms maximizes the predictive ability of each factor, allowing for an individualized characterization of risk compared with risk categories or probability tables.

Another approach relies of characterization and analysis of the cancer tissue obtained from a patient. Clinical data is integrated with an analysis of each patient’s cancer using spatial analysis of tissue histology and examining molecular biomarkers, such as androgen receptor, associated with disease progression. This approach represents a cutting edge of diagnostic science, sometimes termed, “Personalized Medciine”. The concept that one can individualize cancer therpay based on specific tumor characteristics is attractive but needs to be proven before being widely adapted. As of now, there is little evidence to support it and no guidelines or professional bodies recommending it.

Prostate Dx is one such test. It uses its own method of data analysis derived from a large patient cohort to generate a personalized report that is sent to the physician for discussion with the patient. This processand information remains proprietary and not peer-reviewed. This testing has not been cleared (or reviewed) by the U.S. Food and Drug Administration (FDA) becasue the company has indicated that Prostate Px does not require FDA approval. The test is considered a laboratory developed test (LDT) and is performed in Aureon’s Clinical Laboratory Improvement Act (CLIA)-certified, College of American Pathologists (CAP)-accredited, New York State-regulated laboratory.

Studies are ongoing to improve standardization and to determine whether this test can enhance prediction of prostate cancer recurrence and risk compared with current standard methods. Memorial Sloan-Kettering Cancer Center is currently recruiting candidates for a prospective study to determine if there is a small peptide mass protein pattern in blood that can distinguish men with clinically latent prostate cancer from men with more a more advanced disease state.

William T Lowrance, and Peter T Scardino,Predictive Models for Newly Diagnosed Prostate Cancer Patients

Rev Urol. 2009 Summer; 11(3): 117–126.

Donovan, Michael J., PhD, MD, et al., “Systems Pathology: A Paradigm Shift in the Practice of Diagnostic and Predictive Pathology, Cancer, Vol. 115, No. 13, July 1, 2009, pp. 3078–3084.

Eggener, Scott E., MD, et al., “Comparison of Models to Predict Clinical Failure after Radical Prostatectomy, Cancer, Vol. 115, January 15, 2009, pp. 303-310.

HAYES Update Search, “Prostate Px® (Aureon Laboratories Inc.) for Prediction of Recurrence of Prostate Cancer,” Lansdale, PA: HAYES, Inc., January 6, 2012.

Transformed follicular lymphoma – pro

M Levin, MD — Sun, 02 Sep 2012 15:09:56 +0000

Lay Summary: Transplants for transformed follicular lymphoma are supported by follicular lymphoma (transformed) guidelines of the NCCN. There is trial evidence supporting this approach.

Takvorian and colleagues (1987) studied 49 patients with either high-grade (n = 29), intermediate-grade (n =14) or low-grade (n = 6) lymphoma. All patients were considered to have a poor prognosis either due to relapse (n = 41) or poor prognostic factors (n = 8). These latter 8 patients were in at least partial remission but were considered to be at high-risk for relapse due to a bulky tumor mass, or multiple sites of extranodal involvement. All patients had a good performance status. The common feature of all these patients was that they were responsive to conventional induction therapy such that at the time of HDC, all patients had a minimal disease burden. In fact, 23 patients were considered to be in complete remission. A total of 34 of the 49 patients remained in complete remission for 2 to 52 months post-HDC, which translated into a 65 % probability that patients would remain disease free for greater than 11 months. Two patients died from treatment-related toxicity and relapse occurred in 13 others. All relapses occurred before 11 months. Other earlier studies of HDC had included all patients relapsing from disease, regardless of their performance status or whether the lymphoma was chemo-resistant. In these studies the mortality rate ranged from 20 to 40 % and long-term disease survival was seen in only 20 % of patients. Considering their improved results, the authors suggested that HDC should be a treatment option for patients with relapsing disease but with a minimal tumor burden that is still responsive to chemotherapy.

Schouten et al (1994) reported their findings of 92 patients with low-grade NHL treated with HDC and ASCT. At the time of ASCT, the majority of patients had chemosensitive disease in first or subsequent remission (37 %) or disease with a good response to chemotherapy (49 %). At a median follow-up of 19 months, the progression free survival is 52 %. Patients with complete remission or responding relapse at the time of ASCT had a significantly better progression-free survival compared to patients with refractory disease. Patients with transformed low-grade NHL at ASCT had a very poor outcome. Despite the relatively short follow-up of this study, the data suggested that chemosensitive disease responded better to HDC followed by stem cell transplant than refractory disease at the time of ASCT.

Mills and colleagues (1995) reported the main prognostic factors in 107 patients with relapsed or resistant intermediate- or high-grade NHL who underwent HDC with ASCT. All patients had failed to achieve a complete remission to conventional chemotherapy or had subsequently relapsed. Additionally, there was no bone marrow involvement in any of the patients. Forty-two patients (40 %) had chemoresistant disease at the time of HDC, 55 (51 %) had chemosensitive disease, and 10 (9 %) had untested relapse. At 3 months, 44 patients (41 %) were assessed to be in complete remission, 34 (32 %) were in partial remission and 22 (21 %) showed no response or had progressive disease. There were 7 early procedure-related deaths. Overall survival rate at 5 years is 41 % and progression free survival rate is 35 %. None of the patients who were unresponsive to HDC survived beyond 18 months, whereas at a median follow-up of 34 months, 50 % of the partial responders were alive. Patients with chemosensitive disease, small masses, and ASCT after one line of chemotherapy had the best outcome.

In a randomized clinical trial (The European CUP trial), Schouten, et al. (2003) examined if high-dose therapy (HDT) followed by ASCT is more effective than standard treatment with regard to progression-free survival (PFS) and overall survival (OS) in patients with relapsed follicular NHL; and evaluated the additional value of B-cell purging of the stem-cell graft with regards to PFS and OS. Patients received three cycles of chemotherapy. Responding patients with limited bone marrow infiltration were eligible for random assignment to three further cycles of chemotherapy (C), unpurged HDT (U), or purged HDT (P). A total of 140 patients were registered from 36 centers internationally, and 89 were randomly assigned. Reasons for not randomizing included patient refusal, early progression, or death on induction therapy. With a 69-month median follow-up, the log-rank P value for PFS and OS were 0.0037 and 0.079, respectively. The authors concluded that HDT significantly improves PFS and OS in patients under age of 60 years with recurrent chemosensitive disease. Furthermore, there is no clear evidence of benefit through purging. This is in agreement with the observations of Alvarnas and Forman (2004) who stated that data to justify routine use of hematopoietic stem cell graft purging are insufficient.

In a recent review on stem cell transplantation in follicular lymphoma, Tse, et al. (2004) stated that ASCT or allogeneic stem cell transplantation in first remission remains an investigational procedure.

A 2011 review concludes: “Stem cell transplantation (SCT) including both autologous and allogeneic SCT or experimental agent therapy is considered for recurrent disease.”

Freedman A. Follicular lymphoma: 2011 update on diagnosis and management.Am J Hematol. 2011 Sep;86(9):768-75.

HC Schouten, PJ Bierman, WP Vaughan, A Kessinger, JM Vose, DD Weisenburger, and JO Armitage
Autologous bone marrow transplantation in follicular non-Hodgkin’s lymphoma before and after histologic transformation
Blood 74: 2579-2584.

Novel induction regimens in transplantation for mantle cell lymphoma – pro

M Levin, MD — Sun, 02 Sep 2012 15:00:33 +0000

Lay Summary: Stem cell transplantation is standard of care for mantle cell lymphoma.

Mantle cell lymphoma is a fairly recently identified subtype of non-Hodgkin’s lymphoma. Regarded as a low-grade tumour in previous classifications, it has a median survival of only 36 months and is incurable by current treatment approaches. Widespread disease is usually present at diagnosis involving lymph nodes, spleen, bone marrow and extranodal sites such as the gastrointestinal tract. Initial response rates to treatment are high but the majority of patients relapse within 2 years. There is some evidence that high dose myeloablative chemotherapy and total body irradiation followed by stem cell rescue in first remission may give long-term disease-free survival. Both rituximab and Velcade are being clinically investigated as a part of induction. A recent study that used Rituxan reported good results in comparison with historical controls. 24 patients with newly diagnosed mantle cell lymphoma were treated with four to six courses of DHAP-rituximab followed by autologous stem cell transplantation for patients <65 years. Three-year overall survival (OS) and event free survival (EFS) rates were 69% and 65% respectively, for the 24 patients. In intent-to-treat analysis, 3-year OS and EFS were 75% and 76% for the 17 patients < 65 years old.
This is true even for partial resonses after initial chemotehrapy. A study by the European Mantle Cell Lymphoma Network established autologous stem cell transplant as the standard of care. Patients receiving upfront CHOP or CHOP-like induction, followed by autologous stem cell transplant, had prolonged progression-free survival, compared with those on interferon maintenance (P = .0108).1 The study also showed that patients who achieved complete remission, vs partial remission, had the greatest benefit, although there was a suggestion of benefit even with partial remission. The study was not designed to evaluate overall survival, but a strong trend favored the transplant arm.

A phase II study investigating Velcade in a transplant setting but after induction is ongoing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with an autologous stem cell transplant may allow more chemotherapy to be given so that more cancer cells are killed. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib after combination chemotherapy, monoclonal antibody therapy, and an autologous stem cell transplant may kill any remaining cancer cells or keep the cancer from coming back.

The 2011 NCCN also recommends autologous transplantation after Hyper-CVAD but it does not recommend it after a complete response and after a partial response it recommends on p. MANT-@ a clinical trial, including of autologous or allogeneic transplantation. Curiously on the next page is appears to recommend autologosu or allogeneic transplantation and does not mention a clinical trial. This is corroborated on P. MS-82. I read this as a recommendation for an autologous or allogeneic transplant as consolidation for any responsive mantle cell lymphoma.

http://nccn.org/professionals/physician_gls/PDF/nhl.pdf, 2017

Dreyling M, Lenz G, Hoster E, et al: Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: Results of a prospective randomized trial of the European MCL Network. Blood 105:2677-2684, 2005.

2. Hermine O, Hoster E, Walewski J, et al: Alternating courses of 3x CHOP and 3x DHAP plus rituximab followed by a high dose ARA-C containing myeloablative regimen and autologous stem cell transplantation increases overall survival when compared to 6 courses of CHOP plus rituximab followed by myeloablative radiochemotherapy and ASCT in mantle cell lymphoma: Final analysis of the MCL Younger Trial of the European Mantle Cell Lymphoma Network. 2012 ASH Annual Meeting. Abstract 151.

3. Graf SA, Stevenson PA, Holmberg LA, et al: Rituximab maintenance therapy after autologous stem cell transplantation improves survival of patients with mantle cell lymphoma. 2014 ASH Annual Meeting. Abstract 3985. Presented December 8, 2014.

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]

Kiss TL, Mollee P, Lazarus HM, Lipton JH. Stem cell transplantation for mantle cell lymphoma: if, when and how? Bone Marrow Transplantation. 2005;36:655–661

DE GUIBERT S , Jaccard A, Bernard M, Turlure P, et alRituximab and DHAP followed by intensive therapy with autologous stem-cell transplantation as first-line therapy for mantle cell lymphoma.Haematologica. 2006;91:425-6.

Autologous and allogeneic stem cell transplantation for diffuse large cell lymphoma (NHL) – pro

M Levin, MD — Sun, 02 Sep 2012 14:56:12 +0000

Summary: NHL is currently the second most frequent indication for autologous hematopoietic stem cell transplantation. It is not a useful treatment option for all patients with NHL, but in certain circumstances, autologous stem cell transplantation does provide patients the best opportunity for cure.

Diffuse large-cell lymphoma is the most common form of NHL, and autologous stem cell transplantation has been shown to be beneficial in some subsets with this illness. For patients with diffuse large-cell lymphoma who relapse from a CR but remain chemotherapy-responsive, autologous transplantation is the treatment of choice. The most significant study supporting transplantation is the PARMA study by Philip et al. Patients were randomized to autologous stem cell transplantation versus conventional-dose chemotherapy with dexamethasone, high-dose cytarabine, and cisplatin (DHAP) if the patient responded to two initial cycles of DHAP. The event-free survival at 5 years was 46% for the transplant arm and 12% for the conventional therapy arm (p = 0.001). Overall survival was 53% for transplant and 32% for the conventional therapy group (p = 0.038). In addition to transplant being shown to be beneficial in this group of patients, additional analysis has demonstrated that an initial remission of fewer than 12 months is an adverse prognostic indicator.

There are also trials that have found contradictory results. Reyes et al. in the LNH93-3 trial randomized 370 patients to standard chemotherapy or autologous transplantation after an abbreviated standard-dose induction regimen. They found the 3-year event-free survival for the hematopoietic stem cell transplant group was 41% versus 54% for the standard therapy arm (p = 0.01). Overall survival was also in favor of standard therapy with 63% disease-free survival versus 47% in the transplanted group (p = 0.003) [62]. A trial by Verdonck et al. randomized 69 patients who had achieved a partial response to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) to additional CHOP or autologous bone marrow transplantation. The 4-year event-free survival was 53% for the CHOP arm and 41% for the transplantation arm. Disease-free survival at 4 years was 72% for the CHOP group and 60% for transplantation. The reason for the disrepancy is not well understood but these were smaller studies than the PARMA study.

At the present time, high-risk patients who achieve a CR after a full course of standard-dose chemotherapy and have a high risk for relapse may derive the most benefit from stem cell transplantation. The second accepted group is those who evidence chemoresponsiveness after relapse and this is stated in the NCCN guidelines. No additional trials are planned and the Parma results have been accepted as standard therapy.

2011 NCCN on p. BCEL-6 recommends an autologous transplant.

As far as allogeneic, a recent guideline says: “Allogeneic stem cell transplantation is an option for eligible chemosensitive patients with refractory or relapsed AH-NHL who are not candidates for autologous stem cell transplantation or who have a syngeneic (identical twin) donor.” NCCN BCEL-6(2011) says tha llogeneic transplantation is in selected cases and a note explains that such cases include mobilization faiure and persiistent bone marrow invovlement”. All in all, I consider guidelines to mildy support allogeneic transpalntation for relapsed DLCL.

For patients who failed an autologous transplant, 2012 ESMO guideline says: “Allogeneic stem cell transplantation (allo-SCT) should be considered in selected patients failing autologous stem cell transplantation or with very poor risk factors at relapse”.

Zahid U, Akbar F, Amaraneni A, et al. A Review of Autologous Stem Cell Transplantation in Lymphoma. Curr Hematol Malig Rep. 2017;12(3):217–226. doi:10.1007/s11899-017-0382-1

Vikas Gupta et al, Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns Blood February 24, 2011 vol. 117 no. 8 2307-2318

van Kampen RJW, Canals C, Schouten HC, et al. Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-hodgkin’s lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European group for blood and marrow transplantation registry. J Clin Oncol 2011;29:1342-1348.

Thomson KJ, Morris EC, Bloor A, et al. Favorable long-term survival after reduced-intensity allogeneic transplantation for multiple-relapse aggressive non-hodgkin’s lymphoma. J Clin Oncol 2009;27:426-