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

For Lay summary see here

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.

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

Initial chemotehrapy is recommended, although there is no one superior regimen. The INT-0091 study from the COG reported no benefit with the addition of IE to a standard backbone of vincristine, actinomycin-D, cyclophosphamide, and doxorubicin (VACD) . In the second Intergroup Ewing Sarcoma Study (IESS-2), the addition of 5-fluorouracil (5-FU) failed to improve outcome in this subset of patients. In a phase II trial from the Pediatric Oncology Group, high-dose alkylator therapy with topotecan or topotecan plus cyclophosphamide did not improve patient outcomes; however, the latter combination did show activity against metastatic disease (response rate of 57%).

Primitive neuroepithelial tumors include medulloblastoma, neuroblastoma arising in the central nervous system, ependymoblastoma, or pineoblastoma. All show a similar histology and are principally distinguished by their site of origin. Essentially, medulloblastoma may be considered a cerebellar or posterior fossa PNET while pineoblastoma may be considered a PNET arising in the pineal gland, and neuroblastomas may be considered a central PNET. PNETs have been referred to by different terms depending on their location and extent of neural differentiation: peripheral neuroepithelioma, Askin tumor, adult neuroblastoma, peripheral neuroblastoma, and primitive neuroectodermal tumors. The collective term is primitive neuroectodermal tumors. Ewing’s sarcoma and PNET represent a biological spectrum of the same tumor. Since these tumors exhibit only neuroectodermal markers of differentiation, it has been suggested that they arise from neural crest cells. Because treatment is the same for these tumors, they are also referred to as Ewing’s sarcoma/PNET. With this classification, data from all these tumor types can be pooled for anlaysis. Many patients with metastatic disease at diagnosis respond well to the therapy given to patients with localized disease; however, in most cases the disease is only partially controlled or recurs. Currently there are trials using more intensive therapy with or without stem cell transplant although it is not known if this strategy improves outcome.

• Dose-intensive chemotherapy with growth factor support is not recommended in the first-line treatment of patients with inoperable locally advanced or metastatic soft tissue sarcoma.
• There is insufficient data to support the use of high-dose chemotherapy with autologous bone marrow/stem cell transplantation as first-line treatment in this group of patients.

A January 2008 search of the National Cancer Institute (NCI) PDQ database on ongoing clinical trials identified the following open Phase III randomized studies on PNETs: Phase III study of radiotherapy, high-dose cisplatin, vincristine, and cyclophosphamide, and autologous stem-cell rescue in patients with newly diagnosed medulloblastoma, supratentorial primitive neuroectodermal tumor, or atypical teratoid rhabdoid tumor (SJCRH-SJMB03) Phase III pilot study of induction chemotherapy followed by consolidation myeloablative chemotherapy comprising thiotepa and carboplatin with or without etoposide and autologous hematopoietic stem cell rescue in pediatric patients with previously untreated malignant brain tumors. (NCT00392886) The 2006 National Comprehensive Cancer Care Network Guidelines on Central Nervous System Cancers do not address high-dose chemotherapy with stem-cell support for PNET of the CNS.

• Eligible patients should be encouraged to enter clinical trials assessing novel approaches or compounds.

E. Hendershot Treatment Approaches for Metastatic Ewing’s Sarcoma: A Review of the Literature
Journal of Pediatric Oncology Nursing, November 1, 2005; 22(6): 339 – 352.

Bertuzzi A, Castagna L, Nozza A et al. High-dose chemotherapy in poor-prognosis adult small round-cell tumors: Clinical and molecular results from a prospective study. J Clin Oncol 2002;20(8):2181-2188

O. Oberlin, A. Rey, A. S. Desfachelles, T. Philip, D. Plantaz, C. Schmitt, E. Plouvier, O. Lejars, H. Rubie, P. Terrier, and J. Michon
Impact of High-Dose Busulfan Plus Melphalan As Consolidation in Metastatic Ewing Tumors: A Study by the Societe Francaise des Cancers de l’Enfant
J. Clin. Oncol., August 20, 2006; 24(24): 3997 – 4002.

James S. Miser, Mark D. Krailo, Nancy J. Tarbell, Michael P. Link, Christopher J.H. Fryer, Douglas J. Pritchard, Mark C. Gebhardt, Paul S. Dickman, Elizabeth J. Perlman, Paul A. Meyers, Sarah S. Donaldson, Sheila Moore, Aaron R. Rausen, Teresa J. Vietti, Holcolmbe E. Grier Treatment of Metastatic Ewing’s Sarcoma or Primitive Neuroectodermal Tumor of Bone: Evaluation of Combination Ifosfamide and Etoposide—A Children’s Cancer Group and Pediatric Oncology Group Study Journal of Clinical Oncology, Vol 22, No 14 (July 15), 2004: pp. 2873-2876

Stacey A Kalambakas, Theodore B Moore, Stephen A Feig (2004) Megatherapy and stem cell transplantation for Ewing’s family of tumors: A critical review of current literature
Pediatric Transplantation 8 (s5) , 83–88

Nafisah Al-Faris, Talal Al Harbi, Cristina Goia, Alberto Pappo, John Doyle, Adam Gassas. (2007) Does consolidation with autologous stem cell transplantation improve the outcome of children with metastatic or relapsed Ewing sarcoma?. Pediatric Blood & Cancer 49:2, 190

Barker LM, Pendergrass TW, Sanders JE, et al. Survival after recurrence of Ewing’s sarcoma family of tumors. Journal of Clinical Oncology. 2005;23:4354-4362.

Laurence V, Pierga J-Y, Barthier S, et al. Long-term follow-up of high-dose chemotherapy with autologous stem cell rescue in adults with Ewing’s sarcoma. American Journal of Clinical Oncology . 2005;28:301-309.

Michael Huang and Kenneth Lucas Current Therapeutic Approaches in Metastatic and Recurrent Ewing Sarcoma Sarcoma Volume 2011 (2011).

M. Paulussen et al, Ewing’s sarcoma of the bone: ESMO Clinical Recommendations for diagnosis, treatment and follow-up Ann Oncol (2009) 20 (suppl 4): iv140-iv142.

G. Saeter, . ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of Ewing’s sarcoma of bone, Oxford JournalsMedicine Annals of OncologyVolume14, Issue8Pp. 1167-1168

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

The recommended dose of NEUPOGEN® (filgrastim) for the mobilization of PBPC is 10 mcg/kg/day SC‚ either as a bolus or a continuous infusion. It is recommended that NEUPOGEN® (filgrastim) be given for at least 4 days before the first leukapheresis procedure and continued until the last leukapheresis. This The FDA says, “Although the optimal duration of NEUPOGEN® (filgrastim) administration and leukapheresis schedule have not been established‚ administration of NEUPOGEN® (filgrastim) for 6 to 7 days with leukaphereses on days 5‚ 6‚ and 7 was found to be safe and effective (see Clinical Experience for schedules used in clinical trials). Neutrophil counts should be monitored after 4 days of NEUPOGEN® (filgrastim) ‚ and NEUPOGEN® (filgrastim) dose modification should be considered for those patients who develop a WBC count > 100‚000/mm3.” In none of the studies listed in the Clinical Experience section, was Neupogen used for 14 days for stem cell mobilization.

Clinical studies have used longer administrations, for example, Ria et al, used a 12 day schedule. Nevertheless, the FDA approved dose and schdule are the most common and and there seems to be little reason to prefer a longer schdule.

Bassi Simona et a, A single dose of Pegfilgrastim versus daily Filgrastim to evaluate the mobilization and the engraftment of autologous peripheral hematopoietic progenitors in malignant lymphoma patients candidate for high-dose chemotherapy. Transfusion and Apheresis Science Volume 43, Issue 3 , Pages 321-326, December 2010

Tricot G, Barlogie B, Zangari M, van Rhee F, Hoering A, Szymonifka J, et al. Mobilization of peripheral blood stem cells in myeloma with either pegfilgrastim or filgrastim following chemotherapy. Haematological. 2008;93:1739–1742

R Ria et al, Comparison between filgrastim and lenograstim plus chemotherapy for mobilization of PBPCsBone Marrow Transplantation (2010) 45, 277–281

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.

Arnold S. Freedman Biology and Management of Histologic Transformation of Indolent Lymphoma Hematology 2005 © 2005 The American Society of Hematology

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]

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

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]

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-

In some patients in whom HDC fails, allogeneic HSC transplantation may be a viable option. In this method, myeloablative therapy (chemotherapy and sometimes RT) is followed by the infusion of HSCs from a genetically matched donor. This offers the potential for an immunological antitumor effect from T-cells provided by the HSC donor, which may improve the chances for cure of the disease. Historically, allogeneic transplantation for Hodgkin disease has been considered too high risk for most patients due a high transplant-related mortality. However, evolution of transplant protocols to include less toxic conditioning regimens will likely expand the utility of this option for patients with refractory Hodgkin disease. Allogeneic transplantation for Hodgkin disease should ideally be performed in the context of a clinical trial but is considered standard of care already at this time.

In a review, Mink and Armitage (2001) stated that autologous stem cell transplantation has proven to be beneficial in selected patients with HD. Transplantation appeared to increase event-free survival in patients who failed to enter complete remission with initial therapy. When a patient relapses after a complete remission, transplantation is probably the best option and particularly so if the remission lasted less than 1 year. Transplantation as part of primary therapy for very high-risk patients may be beneficial, and is standard therapy at this time. Lazarus et al (2001) reviewed data from the Autologous Blood and Marrow Transplant Registry (n = 414) to determine relapse, disease-free survival, overall survival, and prognostic factors in patients with relapsed HD. They concluded that autologous hematopoietic stem cell transplantation (autotransplantation) should be considered for patients with HD in first relapse or second remission. This is also the 2011 NCCN recommendation (Hodg-6) as category 3.

NCCN says that allogeneic stem cell transplantation can be used in selected patients; it is a category 3 recommendation (HODG-15).

Mink SA, Armitage JO. High-dose therapy in lymphomas: A review of the current status of allogeneic and autologous stem cell transplantation in Hodgkin’s disease and non-Hodgkin’s lymphoma. Oncologist. 2001;6(3):247-256.

Lazarus HM, Loberiza FR Jr, Zhang MJ, et al. Autotransplants for Hodgkin’s disease in first relapse or second remission: A report from the autologous blood and marrow transplant registry (ABMTR). Bone Marrow Transplant. 2001;27(4):387-396.

Reece DE. Hematopoietic stem cell transplantation in Hodgkin disease. Curr Opin Oncol. 2002;14(2):165-170.

A. Engert et al, Hodgkin’s lymphoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up, On behalf of the ESMO Guidelines Working Ann Oncol (2009) 20 (suppl 4): iv108-iv109.

Ercole Brusamolino, Andrea Bacigalupo, Giovanni Barosi, Giampaolo Biti, Paolo G. Gobbi, Alessandro Levis, Monia Marchetti, Armando Santoro, Pier Luigi Zinzani, and Sante Tura

Classical Hodgkin’s lymphoma in adults: guidelines of the Italian Society of Hematology, the Italian Society of Experimental Hematology, and the Italian Group for Bone Marrow Transplantation on initial work-up, management, and follow-up Haematologica 2009 94: 550-565

Balsalobre P, Díez-Martín JL, Re A, Michieli M, Ribera JM, Canals C, Rosselet A, Conde E, Varela R, Cwynarski K, Gabriel I, Genet P, Guillerm G, Allione B, Ferrant A, Biron P, Espigado I, Serrano D, Sureda A. Autologous stem-cell transplantation in patients with HIV-related lymphoma. Clin Oncol. 2009 May 1;27(13):2192-8.

Canellos GP, Mauch PM. Hematopoietic cell transplantation in classical Hodgkin lymphoma. In: UpToDate, Basow, DS (Ed), UpToDate,Waltham,MA, 2013. Literature review current through March 2013.

Moskowitz AJ, Perales MA, Kewalramani T, et al. Outcomes for patients who fail high dose chemoradiotherapy and autologous stem cell rescue for relapsed and primary refractory Hodgkin lymphoma. Br J Haematol 2009; 146:158.

Sarina B, Castagna L, Farina L, et al. Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood 2010; 115:3671.

Thomson KJ, Peggs KS, Smith P, et al. Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin’s lymphoma following autologous stem cell transplantation. Bone Marrow Transplant 2008; 41:765

Corradini P, Sarina B, Farina L. Allogeneic transplantation for Hodgkin’s lymphoma. Br J Haematol 2011; 152:261

John Kuruvilla et al, How I treat relapsed and refractory Hodgkin lymphoma. Blood April 21, 2011 vol. 117 no. 16 4208-4217